Journal articles on the topic 'Mucopolysaccharidosi'
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1
Kenis, Vladimir M., Leonid V. Gorobets, Alena Yu Dimitrieva, Alisa A. Zhmurova-Kriventsova, Igor O. Bychkov, Galina V. Baydakova, Tatiana V. Markova, and Ekaterina Yu Zakharova. "Mucopolysaccharidosis IVB and sensorineural deafness associated with the CDH23 gene: A unique clinical case." Pediatric Traumatology, Orthopaedics and Reconstructive Surgery 10, no. 3 (September 22, 2022): 285–94. http://dx.doi.org/10.17816/ptors108730.
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BACKROUND: Mucopolysaccharidoses are a group of lysosomal storage diseases belonging to orphan diseases. Certain types of mucopolysaccharides have a typical musculoskeletal findings and radiological changes. The mucopolysaccharidosis IVB is a rare type. Thus, 95% of cases of the mucopolysaccharidosis IV are subtype A.
CLINICAL CASE: Сlinical and radiological changes and genetic examination were performed to a 9-year-old patient with sensorineural deafness who applied to a medical institution with complaints of right hip pain and limping.
DISCUSSION: Based on complaints and radiological changes of the hip joints, the patient was initially diagnosed with LeggCalvePerthes disease. The presence of a symmetrical bilateral process, pathognomonic changes in the acetabulum and femoral heads, and an atypical clinic of LeggCalvePerthes disease made us suspect mucopolysaccharidos. Enzymatic analysis revealed a significant decrease in the beta-D-galactosidase enzyme activity. In addition, two compound heterozygous variants in the GLB1 gene were identified: the pathogenic variant c.808TG, inherited from the father, and an insertion of a mobile genetic element, inherited from the mother. Only one variant in the GLB1 gene was detected in the brother (born in 2009), and none of the above GLB1 variants was detected in the older brother (born in 2003). Moreover, the proband (with clinical mucopolysaccharidos IVB) and his brother (born in 2009) (without mucopolysaccharidos IVB) inherited pathogenic CDH23 variants (c.6992TC and c.805CT) from their mother and father, respectively, which is consistent with their having sensorineural hearing loss.
CONCLUSIONS: The uniqueness of this clinical case is the presence of the rare type of mucopolysaccharidos and the separate genetic cause of sensorineural hearing loss in a single patient. The diagnosis of mucopolysaccharidos IVB in the proband was confirmed by biochemical and molecular genetic tests, and the diagnosis of CDH23-associated sensorineural deafness in the proband and brother (born in 2009) was confirmed by molecular genetic testing.
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MAIER-REDELSPERGER, MICHELINE, MARC-HENRI STERN, and PIERRE MAROTEAUX. "Pink Rings Lymphocyte: A New Cytologic Abnormality Characteristic of Mucopolysaccharidosis Type II (Hunter Disease)." Pediatrics 82, no. 2 (August 1, 1988): 286. http://dx.doi.org/10.1542/peds.82.2.286.
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To the Editor.— Mucopolysaccharidoses are a group of rare hereditary storage disorders characterized by various lysosomal hydrolase deficiencies. Clinical condition, radiologic and ophthalmologic examinations, urinary mucopolysaccharides dosage, and leukocyte morphology are generally sufficient for diagnosis.1 However, a more precise classification may be difficult. We herein describe a new lymphocyte abnormality observed in 9/9 cases of type II (Hunter disease) in only 3/19 cases of other types of mucopolysaccharidoses. Capillary blood was collected from 28 children with mucopolysaccharidosis referred to the pediatric department.
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Al-Mosawi, Aamir Jalal. "Clinical and Radiologic Diagnosis of a Patient with Maroteaux-Lamy Syndrome." Series of Medical Science 1, no. 1 (January 13, 2020): 1–5. http://dx.doi.org/10.54178/2771-0629.2020a1.
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Background: Diagnosis of rare diseases or disorders is understandably challenging because it is unfeasible for practicing physicians to make themselves familiar with hundreds of rare diseases. The diagnosis of rare inherited metabolic syndromes such as mucopolysaccharidoses is additionally complicated by the lack of confirmatory sophisticated laboratory tests in many areas of the world. In the more developed countries, the diagnosis of mucopolysaccharidoses depends on urine tests for excessive mucopolysaccharides and enzyme assays. However, these tests are not easily accessible in countries like Iraq, and the diagnosis has to rely on clinical and radiological findings. Case Report: The clinical and radiologic diagnosis of an Iraqi patient with Maroteaux-Lamy syndrome is described. The clinical diagnosis of the girl with early-onset mucopolysaccharidosis and the abnormalities were recognizable before the age of two. The clinical and radiologic diagnosis was Maroteaux-Lamy syndrome because of the absence of mental retardation and the presence of hepatosplenomegaly. Conclusion: Clinical diagnosis of rare metabolic syndromes like mucopolysaccharidoses requires magnificent clinical skills and huge experience because of the similarity between various types of mucopolysaccharidoses.
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Bassyouni, H. T. "Mucopolysaccharidosis type I: clinical and biochemical study." Eastern Mediterranean Health Journal 6, no. 2-3 (June 15, 2000): 359–66. http://dx.doi.org/10.26719/2000.6.2-3.359.
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Of 1240 outpatients referred to the Human Genetics Clinic between 1997 and 1998, 248 [20%]had inborn errors of metabolism, 36 [14%] of which were diagnosed as mucopolysaccharidoses. Parental consanguinity was present in 82% of these patients. Deficiency of alpha-L-iduronidase [IDUA] enzyme in leukocytes and increased urinary mucopolysaccharides excretion were detected in 17 patients. The urinary spot test for glucosaminoglycans was inconclusive in 4 of the 17 cases. Results showed a correlation between the biochemical enzyme activity in leukocytes, the amount of excreted mucopolysaccharides and the subtype and course of mucopolysaccharidosis type I. We conclude that estimation of IDUA enzyme activity in leukocytes can differentiate between clinically overlapping cases of MPS I and MPS II and given the clinical manifestations of MPS I is a definitive and unequivocal method of diagnosis while the urinary spot test is inconclusive
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Baxi, Kalgi, Ashish Jagati, and Pooja Agarwal. "Mucopolysachharidosis-II: A Rare Case Report." Nepal Journal of Dermatology, Venereology & Leprology 18, no. 1 (October 8, 2020): 80–82. http://dx.doi.org/10.3126/njdvl.v18i1.25996.
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Mucopolysaccharidosis belongs to a group of metabolic disorders caused by absence or defective activity of lysosomal enzymes. Mucopolysaccharides are major components of intercellular connective tissue and defect in their metabolism leads to an accumulation of incompletely degraded mucopolysaccharides in the lysosomes which affect various body systems through enzymatic activity. We present a case of mucopolysaccharidosis type II with hallmark cutaneous features, mild mental retardation associated with radiological changes.
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Durkovic, Jasmina. "Diagnostics of mucopolysaccharidoses presented through the case of sanfilippo syndrome." Srpski arhiv za celokupno lekarstvo 132, no. 5-6 (2004): 174–78. http://dx.doi.org/10.2298/sarh0406174d.
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Mucopolysaccharidoses (MPS) are recessive inheritable, progressive diseases of disordered degradation and storage of acid glucos-aminoglycans. A five-year old child with psychomotor development retardation, which started at his age of two, was presented in our study. Clinical examination showed big head with rough facial features, skeleton deformities and hepatosplenomegaly. The diagnosis Dysostosis epifisealis multiplex was also confirmed by the X-ray examination of skeleton. Karyotype: 46, XY. Mental retardation: IQ-48. Clinically suspected mucopolysaccharidosis called for metabolic screening of first morning urine and the positive toluidine blue test result indicated the increased excretion of mucopolysaccharides. Further enzyme analyses of peripheral blood leucocytes confirmed the heparin sulphate sulphatase deficiency on the basis of which A (MPS III) Sanfilippo syndrome was defined. Our patient was born as a twin sibling. The other sibling is clinically healthy and of normal metabolic screening. It was not possible to define precisely the healthy heterozygote by testing the enzyme activities. A large number of mutations at various loci and big genetic heterogeneity of mucopolysaccharidoses made molecular diagnostics difficult. In the subsequent pregnancy, the mother was recommended prenatal diagnostics by enzyme analysis from the cultured chorionic villus. The prognosis of the presented patient is bad, the course of the disease is progressive and the patient can be expected to die in spastic tetraplegia in the second decade of life. The treatment is symptomatic for the time being.
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Gitzelmann, R., N. U. Bosshard, A. Superti-Furga, M. A. Spycher, J. Briner, U. Wiesmann, H. Lutz, and B. Litschi. "Feline Mucopolysaccharidosis VII Due to β-glucuronidase Deficiency." Veterinary Pathology 31, no. 4 (July 1994): 435–43. http://dx.doi.org/10.1177/030098589403100405.
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A male cat 12–14 weeks old had walking difficulties and an enlarged abdomen. Facial dysmorphism, plump paws, corneal clouding, granulation of neutrophils, vacuolated lymphocytes, and a positive urine test for sulfated glycosaminoglycans suggested mucopolysaccharidosis. Cultured fibroblasts incorporated 35SO4 into mucopolysaccharides more actively than did fibroblasts of a feline control, and degradation was far inferior. Activity of β-glucuronidase was absent in leukocytes and markedly reduced in fibroblasts, thus establishing the diagnosis of mucopolysaccharidosis VII, a disorder previously described in humans, dogs, and mice. Light microscopic examination revealed foam cells in virtually all organs examined, and electron microscopic examination showed pancytic storage of floccular material characteristic of mucopolysaccharides. Stored sphingolipids in the form of zebra bodies were seen in ganglion cells of the central nervous system and in smooth muscle cells of blood vessels. This case represents another animal model of mucopolysaccharidosis VII with the full disease characteristics known in human patients.
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Kiem Hao, Tran, Nguyen Thi Diem Chi, Nguyen Thi Hong Duc, and Nguyen Thi Kim Hoa. "A case study of three patients with mucopolysaccharidoses in Hue Central Hospital." SAGE Open Medical Case Reports 8 (January 2020): 2050313X2093824. http://dx.doi.org/10.1177/2050313x20938245.
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Mucopolysaccharidosis is a group of rare metabolic disorders characterized by a deficiency of enzymes in the degradation of glycosaminoglycans. The incomplete degradation process leads to the accumulation of glycosaminoglycans in lysosomes of various tissues, which interferes with cell function. We report three cases that were classified as Hurler—Mucopolysaccharidosis I, Morquio—Mucopolysaccharidosis IV A, and Maroteaux–Lamy—Mucopolysaccharidosis VI. Clinical presentations of these cases vary, depending on each type of enzyme defect. All the patients appeared healthy at birth, and symptoms appear at around 1 or 2 years. Clinical features, radiological findings, and especially enzyme assays have allowed us to establish a definitive diagnosis in these cases. These cases highlight that abnormal clinical symptoms, such as growth failure, coarse facial features, and joint problems, are key points for further investigation relating to mucopolysaccharidosis disease. However, in low- and middle-income countries, it is difficult to have a definitive diagnosis of one of the mucopolysaccharidoses due to lacking enzyme assays.
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Patel, Prajay, Georgia Antoniou, Damian Clark, David Ketteridge, and Nicole Williams. "Screening for Carpal Tunnel Syndrome in Patients With Mucopolysaccharidosis." Journal of Child Neurology 35, no. 6 (March 11, 2020): 410–17. http://dx.doi.org/10.1177/0883073820904481.
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Mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage diseases with multisystem manifestations, including carpal tunnel syndrome (CTS). This study comprised a systematic review of literature and hospital guidelines addressing the method and frequency of screening for carpal tunnel syndrome in mucopolysaccharidosis patients and a review of carpal tunnel syndrome in patients seen in the multidisciplinary mucopolysaccharidosis clinic of a pediatric hospital, in order to develop screening recommendations. The literature reported the importance of routine carpal tunnel syndrome screening from early childhood in patients with mucopolysaccharidosis I, II, IV, and VI. Screening methods included physical examination, nerve conduction studies, electromyography, and ultrasonography. Ten of 20 mucopolysaccharidosis patients in our series underwent carpal tunnel syndrome surgery. Given the high incidence of carpal tunnel syndrome at a young age in mucopolysaccharidosis, the authors recommend performing physical examination and obtaining patient and caregiver history for carpal tunnel syndrome every 6 months from the time of mucopolysaccharidosis diagnosis, supplemented by annual nerve conduction studies in cases with poor history or equivocal examination.
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Wilkerson, M. J., D. C. Lewis, S. L. Marks, and D. J. Prieur. "Clinical and Morphologic Features of Mucopolysaccharidosis Type II in a Dog: Naturally Occurring Model of Hunter Syndrome." Veterinary Pathology 35, no. 3 (May 1998): 230–33. http://dx.doi.org/10.1177/030098589803500311.
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A 5-year-old male Labrador Retriever had progressive incoordination, visual impairment, and exercise intolerance. Coarse facial features, macrodactylia, unilateral corneal dystrophy, generalized osteopenia, progressive neurologic deterioration, and a positive urine spot test for acid mucopolysaccharides suggested mucopolysaccharidosis. Intracytoplasmic vacuoles were most prevalent in epithelial cells, endothelial cells, and histiocytes of liver, kidney, thyroid gland, and spleen. Ultrastructural examination disclosed electron-lucent floccular to lamellar membrane-bound storage material characteristic of mucopolysaccharides. Periodic acid-Schiff-positive intracytoplasmic material was identified in multiple neurons in the medulla, pontine nucleus, cerebellum, and spinal gray matter horns. Biochemical assays identified a deficiency in iduronate-2-sulfatase (IDS) activity in cultured dermal fibroblasts compared with normal dogs. Hair root analysis for IDS showed that the dam was a carrier of X-linked Hunter syndrome and that a phenotypically normal male littermate of the affected dog was normal. This is the first report of Hunter syndrome or mucopolysaccharidosis type II in a dog.
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Shreevastava, Naveen K., and Arti S. Pandey. "Screening Mentally Retarded Children for Inborn Errors of Metabolism." Journal of Nepal Health Research Council 15, no. 1 (August 13, 2017): 20–25. http://dx.doi.org/10.3126/jnhrc.v15i1.18008.
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Background: Most inborn errors of metabolism result in mental retardation and death due to accumulation of abnormal metabolites in the tissues. The presence of abnormal metabolites in the urine of mentally retarded individuals has been used worldwide for detection of inborn errors of metabolism. The purpose of the study is to determine the prevalence of inborn error of metabolism in mentally retarded children.Methods: Random urine samples were collected from mentally retarded children at two institutes in Kathmandu, and also from 60 normal children from Duwakot, Nepal after obtaining consent from their parents. Urine was then tested for the presence of amino acids, keto-acids, mucopolysaccharides, fructose, glucose and protein using simple qualitative color reactions in the laboratory.Results: The tests detected eight cases of Phenylketonuria, which turned out to be false positive on paper chromatography. Three cases of presence of ketone bodies (acetoacetate), ten cases of α-ketoaciduria, two cases of mucopolysaccharidosis and twelve cases of fructosuria amongst the sixty-two urine samples were also found.Conclusions: Certain aminoacidurias, ketoacidurias and mucopolysaccharidoses might be present in the Nepalese population. Within consideration of errors, the samples tested positive should be evaluated by a higher end method to confirm the utility of these simple and cheap chemical tests.
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Keilmann, A., F. Bendel, S. Nospes, C. Lampe, and A. K. Läßig. "Alterations of mucosa of the larynx and hypopharynx in patients with mucopolysaccharidoses." Journal of Laryngology & Otology 130, no. 2 (December 17, 2015): 194–200. http://dx.doi.org/10.1017/s0022215115003357.
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AbstractObjective:This study aimed to: assess the mucosal alterations of the larynx and hypopharynx typical for mucopolysaccharidoses, in a standardised manner; compare the severity in different subtypes of mucopolysaccharidoses; and monitor the effect of an enzyme replacement therapy.Methods:A classification for mucosal alterations of the larynx and hypopharynx was developed and utilised in 55 patients with mucopolysaccharidoses. Fifteen patients who started treatment with enzyme replacement therapy were followed longitudinally.Results:The most severe alterations were seen in the posterior region of the larynx and the arytenoids, and in the region of the false vocal folds. The alterations were most severe in patients with mucopolysaccharidosis II. No clear trend was observed in the patients who received enzyme replacement therapy.Conclusion:Quantification of mucosal alterations of the hypopharynx and larynx in mucopolysaccharidoses patients can provide information about the disease's natural process and about the efficacy of enzyme replacement therapy.
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Clarke, Lorne A., Patricia Dickson, N. Matthew Ellinwood, and Terri L. Klein. "Newborn Screening for Mucopolysaccharidosis I: Moving Forward Learning from Experience." International Journal of Neonatal Screening 6, no. 4 (November 19, 2020): 91. http://dx.doi.org/10.3390/ijns6040091.
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There have been significant advances allowing for the integration of mucopolysaccharidosis I into newborn screening programs. Initial experiences using a single-tier approach for this disorder have highlighted shortcomings that require immediate remediation. The recent evaluation of a second-tier biomarker integrated into the MPS I newborn screening protocol has been demonstrated to greatly improve the precision and predictive value of newborn screening for this disorder. This commentary urges newborn screening programs to learn from these experiences and improve newborn screening for mucopolysaccharidosis I and future mucopolysaccharidoses newborn screening programs by implementation of a second-tier biomarker analyte.
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Osipova, L. A., L. M. Kuzenkova, L. S. Namazova-Baranova, A. K. Gevorkyan, T. V. Podkletnova, and N. D. Vashakmadze. "Sanfilippo Syndrome." Annals of the Russian academy of medical sciences 70, no. 4 (September 28, 2015): 419–27. http://dx.doi.org/10.15690/vramn.v70.i4.1407.
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Sanfilippo syndrome (mucopolysaccharidosis type III) is a lysosomal disorder caused by a defect in the catabolism of heparan sulfate. Mucopolysaccharidosis type III is the most common type of all mucopolysaccharidoses. The pathogenic basis of the disease consists of the storage of undegraded substrate in the central nervous system. Progressive cognitive decline resulting in dementia and behavioural abnormalities are the main clinical characteristics of Sanfilippo syndrome. Mucopolysaccharidosis type III may be misdiagnosed as other forms of developmental delay, attention deficit/hyperactivity disorder and autistic spectrum disorders because of lack of somatic symptoms, presence of mild and atypical forms of the disease. Patients with Sanfilippo syndrome may have comparatively low urinary glycosaminoglycans levels resulting in false negative urinary assay. Definitive diagnosis is made by enzyme assay on leucocytes and cultured fibroblasts. There is currently no effective treatment of mucopolysaccharidosis type III, though ongoing researches of gene, substrate reduction and intrathecal enzyme replacement therapies expect getting curative method to alter devasting damage of central nervous system in near future.
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Barik, Kanal Lal, Prabhat Kumar, Tark Nath Ghosh, Sangita De, and Samit Basu. "Sanfilippo Disease." Journal of Nepal Paediatric Society 32, no. 3 (February 24, 2013): 263–65. http://dx.doi.org/10.3126/jnps.v32i3.6117.
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Sanfilippo disease is a type of Mucopolysaccharidosis, a hereditary progressive disease caused by mutation of gene for degradation of acid mucopolysaccharides. Early detection of this rare disease would enable screening and genetic counseling for asymptomatic family members. DOI: http://dx.doi.org/10.3126/jnps.v32i3.6117 J. Nepal Paediatr. SocVol.32(3) 2012 263-265
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Wani, Arshad Iqbal, Khalid J. Farooqi, Mir Iftikhar Bashir, Shahnaz Ahmad Mir, and Shariq Rashid Masoodi. "Mucopolysaccharidosis: Clinical and Radiological Aspects." JMS SKIMS 15, no. 1 (June 11, 2012): 54–56. http://dx.doi.org/10.33883/jms.v15i1.115.
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Mucopolysaccharidosis (MPS) refers to a group of genetic disorder characterized by excessive accumulation of mucopolysaccharides secondary to deficiencies in specific enzymes. It produces characteristic skeletal abnormalities collectively termed as “dysostosis multiplex”. Here we describe a young female child with classical radiological features of MPS on plain radiographs. JMS 2012;15(1):54-56.
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Penso, Dorothy E. "The Mucopolysaccharidoses: Classification, Symptoms and the Role of the Occupational Therapist." British Journal of Occupational Therapy 55, no. 2 (February 1992): 44–48. http://dx.doi.org/10.1177/030802269205500203.
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The mucopolysaccharidoses are a group of inherited diseases characterised by the abnormal storage of mucopolysaccharides in the tissues. Affected children manifest varying degrees of physical, intellectual and behavioural symptoms. In order to implement the most effective forms of therapy, counselling and advice to affected families, occupational therapists must be aware of the nature of the disorders and their progression and prognosis.
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Malla, KK, T. Malla, S. Basnet, KS Rao, PK Tiwari, A. Ghosh, and N. KC. "Morquio Syndrome in Two Siblings: A Case Report." Journal of Nepal Paediatric Society 31, no. 1 (January 12, 2011): 68–71. http://dx.doi.org/10.3126/jnps.v31i1.3541.
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Morquio syndrome is a rare inherited autosomal recessive disorder characterized by the accumulation of mucopolysaccharides (glycosaminoglycans) in various body tissues. It is rare cause of dwarfism. Many pediatricians therefore are unlikely to see this case hence may miss the diagnosis due to lack of experience. With this view we report two siblings with this dwarfism highlighting the classical clinical and radiological presentation. Key words: Mucopolysaccharidosis; Morquio syndrome DOI: 10.3126/jnps.v31i1.3541J Nep Paedtr Soc 2010;31(1):68-71
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de Jong, J. G. N., J. J. F. Hasselman, A. A. J. van Landeghem, H. L. Vader, and R. A. Wevers. "The spot test is not a reliable screening procedure for mucopolysaccharidoses." Clinical Chemistry 37, no. 4 (April 1, 1991): 572–75. http://dx.doi.org/10.1093/clinchem/37.4.572.
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Abstract To check the reliability of the Ames MPS paper spot test, which is based on the Azure A dye, we sent a series of urine samples to three laboratories where the spot test is part of the metabolic screening for mucopolysaccharidoses. In these laboratories false-negative results ranged between 19% and 35% and false-positive results ranged between 12% and 29% of all samples submitted. In contrast, the quantitative dimethylmethylene blue test (Clin Chem 1989;35:1472-7) detected an increased glycosaminoglycan content in all urine samples from mucopolysaccharidosis patients and gave no false-positive results. In the latter procedure, glycosaminoglycan content is expressed per millimole of creatinine, and age-dependent reference values are used. We conclude that the Ames spot test and other spot tests are unreliable as a screening procedure for mucopolysaccharidoses and should not be used to screen for these diseases.
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Fesslová, Vlasta, Paola Corti, Giovanna Sersale, Attilio Rovelli, Pierluigi Russo, Savina Mannarino, Gianfranco Butera, and Rossella Parini. "The natural course and the impact of therapies of cardiac involvement in the mucopolysaccharidoses." Cardiology in the Young 19, no. 2 (April 2009): 170–78. http://dx.doi.org/10.1017/s1047951109003576.
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AbstractObjectiveTo analyze cardiac involvement and its progression in mucopolysaccharidoses, and to assess the short term impact of new therapeutic strategies.Patients and methodsWe studied echocardiographically 57 patients with various types of mucopolysaccharidoses, specifically types I, II, III, IV and VI, with a median age at the diagnosis of cardiac involvement of 5 years, following them for a median of 4.6 years, with a range from 0.9 to 21.2 years. We used a scoring system, along with the so-called delta score, to quantify the severity of involvement at baseline and at last examination, and to chart their progression over time.ResultsCases with cardiac involvement increased from 59.6% to 87.3% at the last examination. The scores increased with age, and were significantly different according to the specific type of mucopolysaccharidosis. Involvement of the mitral valve was most common, often associated with an aortic valvar anomaly and/or left ventricular hypertrophy. Patients with the first and second types had more severe involvement than those with the third or fourth types. Patients undergoing transplantation of haematopoietic stem cells seem to stabilize after an initial worsening while, in contrast, we were unable to demonstrate an effect of enzyme replacement therapy on the progression of the cardiac disease, possibly because those receiving such treatment had a higher median age, more severe cardiac disease and shorter follow-up.ConclusionsCardiac involvement was present early in more than a half of the patients identified as having mucopolysaccharidosis, and generally progressed, being more frequent and severe in the first and second types of the disease. Longer follow-up is needed to demonstrate any significant improvement induced by new therapies.
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Encarnacion, Carlos O., Dustin Hang, Michael Earing, and Michael E. Mitchell. "Mucopolysaccharidoses Causing Valvular Heart Disease: Report and Review of Surgical Management." World Journal for Pediatric and Congenital Heart Surgery 11, no. 4 (April 19, 2017): NP22—NP24. http://dx.doi.org/10.1177/2150135117690105.
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Mucopolysaccharidosis type I is a genetic disorder with impaired glycosaminoglycan degradation. Cardiac pathologic involvement in this subset of patients is predominantly valvular heart disease. Valvular heart disease seen in these patients will most likely require surgical intervention in their lifetime. Only a limited amount of reports are dedicated to the cardiac surgical management of mucopolysaccharidoses. We present the case of a 32-year-old female with Hurler-Scheie syndrome who required multiple valve replacements due to progression of valvular dysfunction and decline in the quality of life. Multidisciplinary evaluation and discussion early are crucial for quality of life optimization in this cohort of patients.
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Parashari, Umesh Chandra, Sachin Khanduri, Samarjit Bhadury, and Sugandha Rawat. "Roentgenographic diagnosis of mucopolysaccharidosis with particular reference to Morquio syndrome." South African Journal of Radiology 16, no. 1 (February 7, 2012): 32–34. http://dx.doi.org/10.4102/sajr.v16i1.233.
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Mucopolysaccharidosis (MPS) comprises a group of conditions associated with an abnormality in glycoprotein or mucopolysaccharides metabolism. Types of MPS identified are MPS I-H (Hurler's syndrome, gargoylism), MPS II (Hunter's syndrome), MPS III (Sanfilippo's syndrome), MPS IV (Morquio-Brailsford syndrome), MPS I-S (Scheie's syndrome) and MPS VI (Maroteaux-Lamy syndrome). The Hunter type is inherited as an X-linked recessive; the others are autosomal recessive. Patients with MPS IV can usually be clinically distinguished from patients with other forms of MPS; their intelligence is unimpaired, in contrast with other forms of MPS. Husler coined the term dysostosis multiplex to describe the skeletal findings.
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Hashimoto, Ayako, Tadayuki Kumagai, and Hiroyuki Mineta. "Hunter Syndrome Diagnosed by Otorhinolaryngologist." Case Reports in Otolaryngology 2018 (2018): 1–4. http://dx.doi.org/10.1155/2018/4252696.
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Hunter syndrome is a lysosomal disease characterized by deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S). It has an estimated incidence of approximately 1 in 1,62,000 live male births. We report a case of Hunter syndrome diagnosed by an otorhinolaryngologist. To our knowledge, this is the first study diagnosed by an otorhinolaryngologist despite the fact that otorhinolaryngological symptoms manifest at a young age in this disease. The patient was a 4-year-old boy. He underwent adenotonsillectomy. Intubation was difficult, and he had some symptoms which are reasonable as a mucopolysaccharidosis. The otorhinolaryngologist should play an integral role in the multidisciplinary approach to the diagnosis and management of many children with MPS (mucopolysaccharidoses) disorders.
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Wang, Ping, Carol Margolis, Gloria Lin, Elizabeth L. Buza, Scott Quick, Karthik Raj, Rachel Han, and Urs Giger. "Mucopolysaccharidosis Type VI in a Great Dane Caused by a Nonsense Mutation in the ARSB Gene." Veterinary Pathology 55, no. 2 (November 20, 2017): 286–93. http://dx.doi.org/10.1177/0300985817732115.
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Mucopolysaccharidoses are inherited metabolic disorders that result from a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans. Lysosomal glycosaminoglycan accumulation results in cell and organ dysfunction. This study characterized the phenotype and genotype of mucopolysaccharidosis VI in a Great Dane puppy with clinical signs of stunted growth, facial dysmorphia, skeletal deformities, corneal opacities, and increased respiratory sounds. Clinical and pathologic evaluations, urine glycosaminoglycan analyses, lysosomal enzyme assays, and ARSB sequencing were performed. The urine mucopolysaccharide spot test was strongly positive predominantly due to the accumulation of dermatan sulfate. Enzyme assays in leukocytes and tissues indicated a deficiency of arylsulfatase B (ARSB) activity. Histologic examination revealed cytoplasmic vacuoles in many tissues. Analysis of the exonic ARSB DNA sequences from the affected puppy compared to the published canine genome sequence revealed a homozygous nonsense mutation (c.295C>T) in exon 1, replacing glutamine with a premature stop codon (p.Gln99*), predicting no enzyme synthesis. A polymerase chain reaction–based restriction fragment length polymorphism test was established to assist with the clinical diagnosis and breeding of Great Danes. This genotyping test revealed that the clinically healthy parents and some other relatives of the puppy were heterozygous for the mutant allele, but all 200 clinically healthy dogs screened including 15 Great Danes were homozygous for the normal allele. This ARSB mutation is the fourth identified genetic variant causing canine mucopolysaccharidosis VI. Mucopolysaccharidosis VI is the first lysosomal storage disorder described in Great Danes but does not appear to be widespread in this breed.
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Asumda, Faizal Z., Jessica A. Kraker, Sarah C. Thomas, Joseph Maleszewski, Edwin M. Stone, Brendan C. Lanpher, and Lisa A. Schimmenti. "Left-sided valvular heart disease and retinopathy in a 38-year-old woman with attenuated mucopolysaccharidosis: a case report." Therapeutic Advances in Rare Disease 4 (January 2023): 263300402211459. http://dx.doi.org/10.1177/26330040221145945.
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Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders caused by deficient levels and/or activity of glycosaminoglycan (GAG)-degradative enzymes. MPS are characterized by accumulation of the mucopolysaccharides heparan sulfate, dermatan sulfate, keratan sulfate, or chondroitin sulfate in tissues. We report the case of a 38-year-old woman with a history of joint restriction and retinitis pigmentosa who developed bivalvular heart failure requiring surgery. It was not until pathological examination of surgically excised valvular tissue that a diagnosis of MPS I was made. Her musculoskeletal and ophthalmologic symptoms, when placed in the context of MPS I, painted the diagnostic picture of a genetic syndrome that was overlooked until a diagnosis was made in late middle age. Plain Language Summary A 38-year-old woman with heart failure had heart valve surgery. Examining her cardiac valve tissue under the microscope suggested a metabolic disorder called mucopolysaccharidosis type I (MPS I). MPS I is due to defective breakdown of sugar molecules (called glycosaminoglycans or GAGs for short) in the body which then can accumulate, causing dysfunction. Our patient had short stature, a curved spine, stiff joints, and a degenerative eye disease called retinitis pigmentosa, all of which were due to her undiagnosed MPS I. Most patients with MPS I are discovered on newborn screening when they are babies, or at very young ages due to severe symptoms related to the disease. Our patient had a form of MPS I that was less severe, and the first symptom she received medical care for was her eye symptoms. A diagnosis of MPS I made in middle adulthood is unusual for MPS I, and so is an important learning case for providers as there were clues hidden in her medical history that suggested a genetic or inherited syndrome. Our genetics specialists were able to make a definitive diagnosis of MPS I and begin treatment with enzyme replacement therapy, as well as provide information for the patient about her risk of passing this disease on to children.
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Benmansour, Abdelmadjid. "Mucopolysaccharidoses." Batna Journal of Medical Sciences (BJMS) 2, no. 1 (June 30, 2015): 40–44. http://dx.doi.org/10.48087/bjmstf.2015.2110.
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Les Mucopolysaccharidoses (MPS) sont des maladies héréditaires dues à un défaut enzymatique { l’origine de dépôts de glycosaminoglycanes (mucopolysaccharides) au niveau des lysosomes. Ces dépôts vont se retrouver au niveau de tous les organes de façon plus ou moins importante avec des manifestations plus ou moins précoces et plus ou moins parlantes selon le taux de l’activité résiduelle au niveau des organes atteints.Il y a 7 différents types de mucopolysaccharidoses; Certains signes cliniques sont retrouvés en commun chez la plupart de ces maladies en particulier les organomégalies et l’atteinte osseuse. D’autres sont plus spécifiques chez certaines avec une atteinte cérébrale prédominante telle la MPS III (maladie de San Filippo).Elles font l’objet de très nombreuses recherches et des traitements sont possibles avec des résultats encourageants surtout si le traitement est entrepris précocement. Il y a des traitements adjuvants : physiothérapie, médicamenteux, chirurgie cardiaque, oculaire selon le cas. Il existe un traitement spécifique : la greffe de moelle pour certaines des MPS, et un traitement de substitution enzymatique également pour certaines MPS.Plus récemment, des molécules chaperonnes ont été utilisées pour obtenir une augmentation de l’activité résiduelle et dernièrement un traitement par thérapie génique est en cours dévaluation dans plusieurs centres.
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Sheth, Sharvin, and Amit Jhala. "Thoracolumbar kyphosis in siblings of Mucopolysaccharidosis: A case report." Journal of Clinical Orthopaedics 7, no. 1 (2022): 116–21. http://dx.doi.org/10.13107/jcorth.2022.v07i01.491.
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Mucopolysaccharidosis (MPS) is a group of inherited metabolic disorders caused due to abnormal storage of mucopolysaccharides in different tissues of the body. They are autosomal recessive disorders, except MPS II which has an X-linked recessive pattern. Musculoskeletal manifestations occur due to disturbance in bone remodeling and improper development of ossification centers. Thoracolumbar kyphosis is the most common spinal pathology resulting from abnormal vertebral end plate ossification and growth arrest as well as hypotonia and spinal musculature imbalance. The increased life span as a result of medical treatment and lack of osseous penetration of enzyme replacement has raised the issue of thoracolumbar dysplasia and resultant deformity. Here, we discuss a case report of progressive thoracolumbar spinal deformity in two siblings suffering from MPS who underwent spine deformity correction surgeries, and literature review for the same.
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Desjobert, A., and L. Larget-Piet. "Variations in urinary mucopolysaccharides after injection of fibroblasts into patients with mucopolysaccharidoses." Clinical Chemistry 33, no. 10 (October 1, 1987): 1879–82. http://dx.doi.org/10.1093/clinchem/33.10.1879.
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Vasilev, Filipp, Aitalina Sukhomyasova, and Takanobu Otomo. "Mucopolysaccharidosis-Plus Syndrome." International Journal of Molecular Sciences 21, no. 2 (January 9, 2020): 421. http://dx.doi.org/10.3390/ijms21020421.
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Previously, we reported a novel disease of impaired glycosaminoglycans (GAGs) metabolism without deficiency of known lysosomal enzymes—mucopolysaccharidosis-plus syndrome (MPSPS). MPSPS, whose pathophysiology is not elucidated, is an autosomal recessive multisystem disorder caused by a specific mutation p.R498W in the VPS33A gene. VPS33A functions in endocytic and autophagic pathways, but p.R498W mutation did not affect both of these pathways in the patient’s skin fibroblast. Nineteen patients with MPSPS have been identified: seventeen patients were found among the Yakut population (Russia) and two patients from Turkey. Clinical features of MPSPS patients are similar to conventional mucopolysaccharidoses (MPS). In addition to typical symptoms for conventional MPS, MPSPS patients developed other features such as congenital heart defects, renal and hematopoietic disorders. Diagnosis generally requires evidence of clinical picture similar to MPS and molecular genetic testing. Disease is very severe, prognosis is unfavorable and most of patients died at age of 10–20 months. Currently there is no specific therapy for this disease and clinical management is limited to supportive and symptomatic treatment.
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Gorbunova, Victoria N., and Natalia V. Buchinskaia. "Lysosomal storage diseases: mucopolysaccharidosis type I and II." Pediatrician (St. Petersburg) 12, no. 3 (October 13, 2021): 69–83. http://dx.doi.org/10.17816/ped12369-83.
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Mucopolysaccharidosis (MPS) are a genetically heterogeneous group of rare monogenic metabolic diseases associated with hereditary insufficiency of lysosomal enzymes involved in the catabolism of glycosaminoglycans, or mucopolysaccharides. The pathogenesis of MPS is due to the accumulation of non-cleaved glycosaminoglycans in lysosomes, which can destroy cells. All MPS are characterized by a polysystemic manifestation, the simultaneous involvement of many organs and tissues in the pathological process, first of all, connective tissues, bones and cartilaginous. This review presents the epidemiology, clinical, biochemical, and molecular genetic characteristics of MPS types I and II, caused by the recessive mutations in the alpha-L-iduronidase and iduronate-2-sulfatase genes, respectively, and by the accumulation of dermatan and heparan sulfate. Each of these diseases is characterized by clinical polymorphism, especially observed in MPS I, which often manifests in a severe form of Hurler syndrome, but can also occur in a milder form of Scheie syndrome. Currently, there is an increased interest in MPS in the world due to the identification of the spectrum and frequencies of mutations in theIDUAandIDSgenes in various populations, including in Russia, and the practical availability of methods for individual molecular diagnostics. The description of the existing experimental models, their role in the study of the biochemical basis of the pathogenesis of these severe hereditary diseases and the development of various therapeutic approaches are given. Discusses the possibility of early diagnosis of MPS I and II types based on neonatal screening in order to increase the effectiveness of their prevention and treatment, as well as the advantages and disadvantages of the main approaches to the treatment of these serious diseases, such as hematopoietic stem cell transplantation, enzyme replacement and substrate-reducing therapy. A clinical example of a combination therapy for a severe form of mucopolysaccharidosis type I Hurler syndrome is presented
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Anandan, Ajay Kumar, and P. Sharanya. "Mucopolysaccharidosis and Anesthetic Challenges." Indian Journal of Anesthesia and Analgesia 6, no. 5 (P-2) (2019): 1863–65. http://dx.doi.org/10.21088/ijaa.2349.8471.6519.54.
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van den Eeden, Yannick N. T., Niklas Unter Ecker, Holger Kleinertz, Thorsten Gehrke, and Tobias M. Ballhause. "Total Hip Arthroplasty in a Patient with Mucopolysaccharidosis Type IVB." Case Reports in Orthopedics 2021 (April 28, 2021): 1–8. http://dx.doi.org/10.1155/2021/5584408.
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Introduction. Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive lysosomal storage disease, characterized by abnormal metabolism of glycosaminoglycans associated with specific skeletal deformities, also known as dysostosis multiplex. Case Presentation. We present the case of a 23-year-old patient with advanced osteonecrosis of the femoral head (ONFH) on both sides due to Morquio syndrome. A diagnosis of mucopolysaccharidosis type IVB was made after extensive genetic profiling. The patient had the condition for a long time. At 7 years old, the patient was treated with bilateral pelvic Salter’s osteotomy. Afterward, the patient was able to walk freely but could never take part in sports. At 22 years old, pain in the hip increased, and magnetic resonance imaging showed a bilateral femur head necrosis. Hence, the patient underwent cementless total hip arthroplasty (THA). Intraoperatively, a periprosthetic fracture occurred. Therefore, revision surgery with internal fixation was performed on the next day. Postoperatively, a weight-bearing restriction of 20 kg on the left leg was imposed for 6 weeks. The patient made a full recovery and was able to move without residual complaints. Annual orthopedic evaluation in patients treated with surgical intervention is recommended. Discussion. Orthopedic challenges for mucopolysaccharidoses and corresponding bone alterations, known as dysostosis multiplex, involving trunk and limbs with typical radiological findings have been well described. The hip is invariably involved, with dysplasia affecting the femoral neck (coxa valga), femoral epiphysis (loss of sphericity, osteonecrosis), and a flared hypoplastic iliac wing. Symptomatic therapy consists, on the one hand, of a surgical procedure and, on the other hand, a variety of supportive measures. However, the management of joint replacement in lysosomal storage diseases has not been well reported. All patients with MPS should be considered at high risk for surgical intervention requiring anesthesia because of airway and cardiac disease manifestations. In the case of a need for THA, we recommend cemented stem fixation because of the overall poor bone quality in patients with Morquio syndrome.
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Sofronova, Viktoriia, Rina Iwata, Takuya Moriya, Kiunniai Loskutova, Elizaveta Gurinova, Mairanush Chernova, Anastasia Timofeeva, et al. "Hematopoietic Disorders, Renal Impairment and Growth in Mucopolysaccharidosis-Plus Syndrome." International Journal of Molecular Sciences 23, no. 10 (May 23, 2022): 5851. http://dx.doi.org/10.3390/ijms23105851.
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Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders (LSD) characterized by the excessive accumulation of glycosaminoglycans (GAG). Conventional MPS, caused by inborn deficiencies of lysosomal enzymes involved in GAG degradation, display various multisystemic symptoms—including progressive neurological complications, ophthalmological disorders, hearing loss, gastrointestinal and hepatobiliary issues, cardiorespiratory problems, bone and joint abnormalities, dwarfism, and coarse facial features. Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease caused by a mutation in the endo-lysosomal tethering protein VPS33A, shows additional renal and hematopoietic abnormalities (“Plus symptoms”) uncommon in conventional MPS. Here, we analyze data from biochemical, histological, and physical examinations—particularly of blood counts and kidney function—to further characterize the clinical phenotype of MPSPS. A series of blood tests indicate hematopoietic symptoms including progressive anemia and thrombocytopenia, which correlate with histological observations of hypoplastic bone marrow. High urinary excretion of protein (caused by impairments in renal filtration), hypoalbuminemia, and elevated levels of creatinine, cholesterol, and uric acid indicate renal dysfunction. Histological analyses of MPSPS kidneys similarly suggest the extensive destruction of glomerular structures by foamy podocytes. Height and weight did not significantly deviate from the average, but in some cases, growth began to decline at around six months or one year of age.
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Amartino, Hernan. "Hunter Syndrome (Mucopolysaccharidosis II) – The Signs and Symptoms a Neurologist Needs to Know." European Neurological Review 10, no. 01 (2015): 90. http://dx.doi.org/10.17925/enr.2015.10.01.90.
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Hunter syndrome (mucopolysaccharidosis II) is a rare X-linked lysosomal storage disease caused by deficiency of the enzyme iduronate-2-sulfatase. The condition is one of a group of disorders, the mucopolysaccharidoses, which all result in accumulation of glycosaminoglycans. Hunter syndrome is a chronic progressive disorder whose clinical manifestations vary widely in severity and involve multiple organs and tissues. In addition to developing somatic symptoms, patients having the neuronopathic form of the disease also display developmental delay and cognitive impairment in early childhood that progressively worsens and that is severely life-limiting. Patients are at risk of developing secondary neurological manifestations, including hydrocephalus, vision and hearing loss, carpal tunnel syndrome and spinal cord compression. Common findings from brain magnetic resonance imaging (MRI) scans and at autopsy include neurodegenerative changes in white matter, the corpus callosum and basal ganglia; enlargement of periventricular spaces; ventriculomegaly; closed cephaloceles; and tissue atrophy. Though at present there is no specific treatment for the neurodegenerative aspects of the disease, hydrocephalus, carpal tunnel syndrome and spinal cord compression can be managed surgically. Patients who have Hunter syndrome should receive coordinated care from a multidisciplinary team: in light of the extensive neurological symptoms of the disease, neurologists play an important role in the diagnosis and management of this condition.
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Álvarez, J., Carolina Herrero Filgueira, Alexandre González, Cristóbal Colón Mejeras, Andrés Beiras Iglesias, Shunji Tomatsu, José Blanco Méndez, Asteria Luzardo Álvarez, María Couce, and Francisco Otero Espinar. "Enzyme-Loaded Gel Core Nanostructured Lipid Carriers to Improve Treatment of Lysosomal Storage Diseases: Formulation and In Vitro Cellular Studies of Elosulfase Alfa-Loaded Systems." Pharmaceutics 11, no. 10 (October 11, 2019): 522. http://dx.doi.org/10.3390/pharmaceutics11100522.
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Mucopolysaccharidosis IVA (Morquio A) is a rare inherited metabolic disease caused by deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS). Until now, treatments employed included hematopoietic stem cell transplantation and enzyme replacement therapy (ERT); the latter being the most commonly used to treat mucopolysaccharidoses, but with serious disadvantages due to rapid degradation and clearance. The purpose of this study was to develop and evaluate the potential of nanostructured lipid carriers (NLCs) by encapsulating elosulfase alfa and preserving its enzyme activity, leading to enhancement of its biological effect in chondrocyte cells. A pegylated elosulfase alfa-loaded NLC was characterized in terms of size, ζ potential, structural lipid composition (DSC and XRD), morphology (TEM microscopy), and stability in human plasma. The final formulation was freeze-dried by selecting the appropriate cryoprotective agent. Viability assays confirmed that NLCs were non-cytotoxic to human fibroblasts. Imaging techniques (confocal and TEM) were used to assess the cellular uptake of NLCs loaded with elosulfase alfa. This study provides evidence that the encapsulated drug exhibits enzyme activity inside the cells. Overall, this study provides a new approach regarding NLCs as a promising delivery system for the encapsulation of elosulfase alfa or other enzymes and the preservation of its activity and stability to be used in enzymatic replacement therapy (ERT).
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Bosshard, N. U., M. Hubler, S. Arnold, J. Briner, M. A. Spycher, H. J. Sommerlade, K. von Figura, and R. Gitzelmann. "Spontaneous Mucolipidosis in a Cat: An Animal Model of Human I-Cell Disease." Veterinary Pathology 33, no. 1 (January 1996): 1–13. http://dx.doi.org/10.1177/030098589603300101.
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A 7-month-old female cat was seen for abnormal facial features and abnormality of gait. Facial dysmorphism, large paws in relation to body size, dysostosis multiplex, and poor growth were noted, and mucopolysaccharidosis was suspected. A negative urine test for sulfated glycosaminoglycans and extreme stiffness of skin indicated a mucolipidosis hitherto unknown in animals. Deficiency of UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) activity was demonstrated in leukocytes and cultured fibroblasts, which had the appearance of inclusion cells (I-cells). Activities of a set of lysosomal hydrolases were abnormally low in fibroblasts and excessive in blood plasma. Postmortem morphology revealed lysosomal inclusions predominantly in fibroblasts but also in endothelial cells and chondrocytes, i.e., in cells of mesenchymal origin. Storage lysosomes contained oligosaccharides, mucopolysaccharides, and lipids. Tissues most affected were bones, cartilage, skin, and other connective tissues such as those in heart valves, aortic wall, and vocal cords. Parenchymal cells of liver and kidney were unaffected, as was skeletal muscle. Only a few of the cerebral cortical neurons had lipid inclusions; in sciatic nerve some axons were affected, but other peripheral nerves were normal. There were striking clinical, biochemical, and morphologic similarities between the disorder in this cat and the human I-cell disease.
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Mashima, Ryuichi, Torayuki Okuyama, and Mari Ohira. "Biomarkers for Lysosomal Storage Disorders with an Emphasis on Mass Spectrometry." International Journal of Molecular Sciences 21, no. 8 (April 14, 2020): 2704. http://dx.doi.org/10.3390/ijms21082704.
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Lysosomal storage disorders (LSDs) are characterized by an accumulation of various substances, such as sphingolipids, mucopolysaccharides, and oligosaccharides. The LSD enzymes responsible for the catabolism are active at acidic pH in the lysosomal compartment. In addition to the classically established lysosomal degradation biochemistry, recent data have suggested that lysosome plays a key role in the autophagy where the fusion of autophagosome and lysosome facilitates the degradation of amino acids. A failure in the lysosomal function leads to a variety of manifestations, including neurovisceral disorders. While affected individuals appear to be normal at birth, they gradually become symptomatic in childhood. Biomarkers for each condition have been well-documented and their proper selection helps to perform accurate clinical diagnoses. Based on the natural history of disorders, it is now evident that the existing treatment becomes most effective when initiated during presymptomatic period. Neonatal screening provides such a platform for inborn error of metabolism in general and is now expanding to LSDs as well. These are implemented in some areas and countries, including Taiwan and the U.S. In this short review, we will discuss several issues on some selected biomarkers for LSDs involving Fabry, Niemann–Pick disease type C, mucopolysaccharidosis, and oligosaccharidosis, with a focus on mass spectrometry application to biomarker discovery and detection.
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Nagao, Kyoko, Cassidy Walter, William J. Parkes, Michael Teixido, Mary C. Theroux, Stacy Szymkowski, Thierry Morlet, and Shunji Tomatsu. "Cochlear implantation in a patient with mucopolysaccharidosis IVA." SAGE Open Medical Case Reports 7 (January 2019): 2050313X1987379. http://dx.doi.org/10.1177/2050313x19873791.
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Mucopolysaccharidosis IVA (OMIM 253000; also known as Morquio A syndrome) is associated with skeletal, airway, and hearing abnormalities. Cochlear implantation is an effective intervention for patients with severe-to-profound hearing loss. Patients can gain substantial improvement in auditory performance, speech perception, and their quality of life from cochlear implantation. Although severe progressive sensorineural hearing loss is a common feature of mucopolysaccharidosis IVA, no detailed description of cochlear implantation for mucopolysaccharidosis IVA has been reported. To review the effectiveness and special considerations associated with cochlear implantation in patients with mucopolysaccharidosis IVA, we here report the case of cochlear implantation in mucopolysaccharidosis IVA by a multidisciplinary team. A retrospective chart review was conducted on a 34-year-old female with mucopolysaccharidosis IVA, who received a cochlear implant. Audiometric thresholds, speech perception scores, and cochlear implant processor mapping information were reviewed during the first 12 months following cochlear implantation. The results of audiological tests indicate improved hearing thresholds as well as remarkable enhancement of speech perception skills over 12 months of cochlear implant use. Cochlear implantation improved auditory performance in a mucopolysaccharidosis IVA patient with postlingually severe-to-profound sensorineural hearing loss. The benefits of cochlear implantation could be meaningful for other Morquio patients with progressive hearing loss, although the risks of surgery and anesthesia should be carefully considered by a multidisciplinary team of experts during the cochlear implant candidacy process.
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Gorbunova, V. N., and N. V. Buchinskaya. "Lysosomal storage diseases. Mucopolysaccharidosis type III, sanfilippo syndrome." Pediatrician (St. Petersburg) 12, no. 4 (December 13, 2021): 69–81. http://dx.doi.org/10.17816/ped12469-81.
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The review describes the clinical, biochemical and molecular genetic characteristics of autosomal recessive mucopolysaccharidosis type III, or Sanfilippo syndrome. This is a genetically heterogeneous group of rare, but similar in nature, diseases caused by a deficiency of one of the four lysosomal enzymes involved in the degradation of heparan sulfate. All types of mucopolysaccharidosis III are characterized by severe degeneration of the central nervous system in combination with mild somatic manifestations, which is explained by the accumulation of high concentrations of heparan sulfate in the lysosomes of various cells, including the central nervous system. The primary biochemical defect in the most common type of mucopolysaccharidosis IIIA, occurring with a frequency of 1 : 105 and presented in 60% of all cases of the disease, is heparan-N-sulfatase, or sulfamidase deficiency. Mucopolysaccharidosis IIIB type occurs twice less often and accounts for about 30% of all cases of Sanfilippo syndrome. It is caused by the presence of inactivating mutations in the lysosomal -N-acetylglucosaminidase gene. Mucopolysaccharidosis IIIC and IIID are 4% and 6%, and occur at frequencies of 0.7 and 1.0 : 106. Mucopolysaccharidosis IIIC is caused by inactivating mutations in the gene of membrane-bound lysosomal acetyl-CoA:-glucosaminid-N-acetyltransferase, or N-acetyltransferase. Mucopolysaccharidosis IIID is based on the deficiency of lysosomal N-acetylglucosamine-6-sulfatase. The role of experimental models in the study of the biochemical basis of the pathogenesis of Sanfilippo syndrome and the development of various therapeutic approaches are discussed. The possibility of neonatal screening, early diagnosis, prevention and pathogenetic therapy of these severe lysosomal diseases are considered. As an example, a clinical case of diagnosis and treatment of a child with type IIIB mucopolysaccharidosis is presented.
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Guevara-Morales, Johana M., Michael Frohbergh, Hector Castro-Abril, Juan J. Vaca-González, Luis A. Barrera, Diego A. Garzón-Alvarado, Edward Schuchman, and Calogera Simonaro. "Growth Plate Pathology in the Mucopolysaccharidosis Type VI Rat Model—An Experimental and Computational Approach." Diagnostics 10, no. 6 (May 31, 2020): 360. http://dx.doi.org/10.3390/diagnostics10060360.
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Background: Mucopolysaccharidoses (MPS) are a group of inherited metabolic diseases caused by impaired function or absence of lysosomal enzymes involved in degradation of glycosaminoglycans. Clinically, MPS are skeletal dysplasias, characterized by cartilage abnormalities and disturbances in the process of endochondral ossification. Histologic abnormalities of growth cartilage have been reported at advanced stages of the disease, but information regarding growth plate pathology progression either in humans or in animal models, as well as its pathophysiology, is limited. Methods: Histological analyses of distal femur growth plates of wild type (WT) and mucopolysaccharidosis type VI (MPS VI) rats at different stages of development were performed, including quantitative data. Experimental findings were then analyzed in a theoretical scenario. Results: Histological evaluation showed a progressive loss of histological architecture within the growth plate. Furthermore, in silico simulation suggest the abnormal cell distribution in the tissue may lead to alterations in biochemical gradients, which may be one of the factors contributing to the growth plate abnormalities observed, highlighting aspects that must be the focus of future experimental works. Conclusion: The results presented shed some light on the progression of growth plate alterations observed in MPS VI and evidence the potentiality of combined theoretical and experimental approaches to better understand pathological scenarios, which is a necessary step to improve the search for novel therapeutic approaches.
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Khaliq, Tanvir, Martin Sadilek, C. Ronald Scott, Frantisek Turecek, and Michael H. Gelb. "Tandem Mass Spectrometry for the Direct Assay of Lysosomal Enzymes in Dried Blood Spots:Application to Screening Newborns for Mucopolysaccharidosis IVA." Clinical Chemistry 57, no. 1 (January 1, 2011): 128–31. http://dx.doi.org/10.1373/clinchem.2010.149880.
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BACKGROUND Treatments are being developed for an increasing number of mucopolysaccharidoses, and early diagnosis is expected to be necessary to maximize the benefits of therapy. Therefore, we developed an assay for N-acetylgalactosamine-6-sulfate sulfatase (GALNS), the enzyme deficient in mucopolysaccharidosis IVA (Morquio A syndrome), that is applicable for clinical diagnosis. METHODS A novel substrate for GALNS was synthesized for a new enzyme activity assay that is based on tandem mass spectrometry and uses dried blood spots (DBSs) as the enzyme source. We optimized the assay conditions, including the substrate concentration, reaction pH, lead formate concentration, incubation time, punch size of the DBS, and mass spectrometer conditions. We also assessed inter- and intraassay variation. RESULTS The assay uses either solid-phase or liquid-phase extraction before analysis by mass spectrometry. An evaluation of blood spots from 90 randomly chosen healthy newborns and 9 patients with Morquio A syndrome showed a well-defined interval between their respective enzyme activities. Inter- and intraassay imprecision was <10%. CONCLUSIONS This tandem mass spectrometry assay requires a minimal number of sample-preparation steps, thus making it easy to implement. The assay has the potential to be adopted for early diagnosis of Morquio A syndrome. We believe this assay could be performed in a multiplex fashion with assays for other lysosomal enzymes.
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Piechnik, Matthew, Paige C. Amendum, Kazuki Sawamoto, Molly Stapleton, Shaukat Khan, Nidhi Fnu, Victor Álvarez, et al. "Sex Difference Leads to Differential Gene Expression Patterns and Therapeutic Efficacy in Mucopolysaccharidosis IVA Murine Model Receiving AAV8 Gene Therapy." International Journal of Molecular Sciences 23, no. 20 (October 21, 2022): 12693. http://dx.doi.org/10.3390/ijms232012693.
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Adeno-associated virus (AAV) vector-based therapies can effectively correct some disease pathology in murine models with mucopolysaccharidoses. However, immunogenicity can limit therapeutic effect as immune responses target capsid proteins, transduced cells, and gene therapy products, ultimately resulting in loss of enzyme activity. Inherent differences in male versus female immune response can significantly impact AAV gene transfer. We aim to investigate sex differences in the immune response to AAV gene therapies in mice with mucopolysaccharidosis IVA (MPS IVA). MPS IVA mice, treated with different AAV vectors expressing human N-acetylgalactosamine 6-sulfate sulfatase (GALNS), demonstrated a more robust antibody response in female mice resulting in subsequent decreased GALNS enzyme activity and less therapeutic efficacy in tissue pathology relative to male mice. Under thyroxine-binding globulin promoter, neutralizing antibody titers in female mice were approximately 4.6-fold higher than in male mice, with GALNS enzyme activity levels approximately 6.8-fold lower. Overall, male mice treated with AAV-based gene therapy showed pathological improvement in the femur and tibial growth plates, ligaments, and articular cartilage as determined by contrasting differences in pathology scores compared to females. Cardiac histology revealed a failure to normalize vacuolation in females, in contrast, to complete correction in male mice. These findings promote the need for further determination of sex-based differences in response to AAV-mediated gene therapy related to developing treatments for MPS IVA.
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Prabhudesai, Anushka, Santosh Kondekar, Namrata Patil, and Surbhi Rathi. "A Clinical Diagnostic Dilemma in Mucopolysaccharidosis." Pediatric Education and Research 7, no. 3 (2019): 119–20. http://dx.doi.org/10.21088/per.2321.1644.7319.7.
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Hristakeva-Atanasova, Desislava, and Under the supervison of Dr Luba Bachvarova. "Mucopolysaccharidosis." Varna Medical Forum 5 (December 10, 2016): 131. http://dx.doi.org/10.14748/vmf.v5i0.1988.
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Guarany, Nicole Ruas, Ana Paula Vanz, Matheus Vernet Machado Bressan Wilke, Daniele Dorneles Bender, Mariana Dumer Borges, Roberto Giugliani, and Ida Vanessa Doederlein Schwartz. "Mucopolysaccharidosis." Journal of Inborn Errors of Metabolism and Screening 3 (February 18, 2015): 232640981561380. http://dx.doi.org/10.1177/2326409815613804.
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Chiu, Cheng-Hui. "Mucopolysaccharidosis." Tzu Chi Medical Journal 23, no. 2 (June 2011): 72. http://dx.doi.org/10.1016/j.tcmj.2011.04.004.
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Gadepalli, Chaitanya, Govind Tol, Karolina M. Stepien, Reena Sharma, and Andrew Bentley. "Salford Mucopolysaccharidosis Airway Score (SMAS): A novel marker of the severity of the airway disease in adult mucopolysaccharidoses." Molecular Genetics and Metabolism 132, no. 2 (February 2021): S41. http://dx.doi.org/10.1016/j.ymgme.2020.12.083.
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Alsafadi, Danyah, Aly Ezzat, Fatima Altamimi, Marwan ElBagoury, Mohammed Olfat, Mohammed Saleh, Sherif Roushdy, and Yahia Aktham. "Mucopolysaccharidosis Type I Disease Prevalence Among Patients With Idiopathic Short Stature in Saudi Arabia: Protocol for a Multicenter Cross-sectional Study." JMIR Research Protocols 10, no. 8 (August 31, 2021): e28619. http://dx.doi.org/10.2196/28619.
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Background Since the underlying cause of idiopathic short stature can indeed be undiagnosed mucopolysaccharidosis type I, it is critical to identify patients with mucopolysaccharidosis type I among screened patients with idiopathic short stature. Objective The primary objective of this study is to determine the prevalence of mucopolysaccharidosis type I disease in a high-risk group (ie, patients with idiopathic short stature). Methods We plan to perform a multicenter, cross-sectional screening study to primarily assess the prevalence of mucopolysaccharidosis type I disease in patients with idiopathic short stature. All eligible patients will be tested after obtaining written informed consent from their parents and guardians. Eligible patients will be recruited over 18 months from specialty care centers for pediatrics and genetics. Results This protocol was approved by the Institutional Review Board of King Fahd Medical City and funded by Sanofi Genzyme Saudi Arabia. We expect to collect data from ≥800 patients, as determined by our sample size calculation. Conclusions Saudi Arabia is the largest country in the Arabian Peninsula; it has a population of more than 28 million people. To date, there are no reliable data regarding the incidence and prevalence of mucopolysaccharidosis type I in Saudi Arabia; therefore, future multicenter studies will be needed. Further, the prevalence of an attenuated form of mucopolysaccharidosis type I is largely underestimated in Saudi Arabia due to the absence of an effective newborn screening program. Therefore, the implementation of a nationwide newborn screening program is essential for the accurate estimation of the burden of mucopolysaccharidosis and the early diagnosis of patients. International Registered Report Identifier (IRRID) PRR1-10.2196/28619
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Middleton, Dana M., Jonathan Y. Li, Steven D. Chen, Leonard E. White, Patricia I. Dickson, N. Matthew Ellinwood, and James M. Provenzale. "Quantitative diffusion tensor imaging analysis does not distinguish pediatric canines with mucopolysaccharidosis I from control canines." Neuroradiology Journal 30, no. 5 (July 13, 2017): 454–60. http://dx.doi.org/10.1177/1971400917718844.
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Purpose We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value. Results No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort. Conclusion The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.
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Alizada, Sevda Aydin, Kamila Ali Agha Aliyeva, Shirkhan Aftandil Musayev, and Elkhan Mammed Rasul Rasulov. "Genetics of Mucopolysaccharidosis Type IV (Morquio Disorder) in Patients from Azerbaijan." Ukraïnsʹkij žurnal medicini, bìologìï ta sportu 7, no. 3 (July 2, 2022): 99–105. http://dx.doi.org/10.26693/jmbs07.03.099.
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Genetic screening in the Azerbaijan Republic for mucopolysaccharidosis disorder has been implemented. The purpose of the work was to study types of mucopolysaccharidosis mutations and discuss ways of disorder prophylaxis in the family with parents of reproductive ages. Materials and methods. Material for studies was collected in the specialized children medical centers in Baku city, Azerbaijan, as well as in the field works in the regions of the Republic for 2018–2022. Patients were chosen during clinical examinations by pediatrician and geneticist. To screen mucopolysaccharidosis disorder a complex of modern molecular-genetic diagnostics methods have been applied. 56 patients were identified in the age varied between six months and 28 years. Gender differentiation was as follows: 15 males and 11 females. Blood sampling was done onto dry blood sample cards. All patients have undergone enzyme analysis for all mucopolysaccharidosis types. Results and discussion. The carried-out screening of enzymatic analysis allowed us to identify 26 patients with the N-aсetylgalaсtosamine-6-sulfat sulfatase enzyme deficit out of disorder suspicious 56 persons. And that was specific for mucopolysaccharidosis type IV A. That counted 46.4% of all studied patients. Seven mutation types in homozygous, double heterozygous (compound) and heterozygous state were identified. All mutations have nucleotide substitution. Practical application of the results is being discussed. Mucopolysaccharidosis type IV frequency was higher than other mucopolysaccharidosis disorder types. In eight patients the level of the enzyme was very low and varied between <0.1 (LOD) μmol/L/h and <0.3 (LOD) μmol/L/h, which is specific for homozygous or double heterozygous state, when norm is ≥2.0 mol/L/h. In 18 patients the activity level of N-aсetylgalaсtosamine-6-sulfate sulfatase enzyme was almost half reduced (<0.6 (LOD) μmol/L/h - <0.1 (LOD)), which speaks to heterozygous state of disorder. Conclusion. Thus, for the first time populational study of mucopolysaccharidosis disorder by means of molecular-genetic modern complex has been carried out. Molecular-genetic analysis allowed our identification of 7 GALNS gene mutation types: 553 C>T, 439 T>A, 1283 A>G, 157 G>A, 463 G-T, 1018 G-T and 443 A>G. These mutations have nucleotide substitutions and have been priory described in references