Mucopolysaccharidosis Type IIIA: Clinical Spectrum and Genotype-Phenotype Correlations
| العنوان: | Mucopolysaccharidosis Type IIIA: Clinical Spectrum and Genotype-Phenotype Correlations |
|---|---|
| المؤلفون: | George J G Ruijter, Otto P. van Diggelen, Dicky J. Halley, Hennie T. Brüggenwirth, Ron A. Wevers, Marlies J. Valstar, Renske Olmer, Ben J. H. M. Poorthuis, Frits A. Wijburg, Sanne Neijs |
| المساهمون: | Paediatric Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Medical Biochemistry, Pediatrics, Clinical Genetics |
| المصدر: | Annals of neurology, 68(6), 876-887. John Wiley and Sons Inc. Annals of Neurology, 68, 876-87 Annals of Neurology, 68(6), 876-887. John Wiley & Sons Inc. Annals of Neurology, 68, 6, pp. 876-87 |
| بيانات النشر: | John Wiley & Sons Inc., 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Pathology, Hydrolases, Mucopolysaccharidosis, DNA Mutational Analysis, Behavioral Symptoms, Kaplan-Meier Estimate, Compound heterozygosity, Gastroenterology, Severity of Illness Index, Cohort Studies, Mucopolysaccharidosis III, Pregnancy, Genotype, Medicine, Missense mutation, Child, Mucopolysaccharidosis Type IIIA, Hearing Disorders, Cells, Cultured, Sanfilippo syndrome, Skin, Middle Aged, Phenotype, Neurology, Child, Preschool, Regression Analysis, Female, Functional Neurogenomics [DCN 2], Adult, Sleep Wake Disorders, medicine.medical_specialty, Adolescent, Vision Disorders, Mucopolysaccharidosis type III, Young Adult, SDG 3 - Good Health and Well-being, Internal medicine, Humans, Genetic Association Studies, Epilepsy, business.industry, Glycostation disorders [IGMD 4], Fibroblasts, medicine.disease, Mutation, Neurology (clinical), business |
| الوصف: | Contains fulltext : 89261.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Mucopolysaccharidosis (MPS) IIIA (Sanfilippo syndrome type A) is a lysosomal storage disorder caused by deficiency of the enzyme sulfamidase. Information on the natural course of MPS IIIA is scarce, but is much needed in view of emerging therapies. METHODS: Clinical history and molecular defects of all 110 MPS IIIA patients identified by enzymatic studies in the Netherlands were collected and included in this study. RESULTS: First clinical signs, mainly consisting of delayed speech development and behavioral problems, were noted between the ages of 1 and 6 years. Other symptoms included sleeping and hearing problems, recurrent upper airway infections, diarrhea, and epilepsy. The clinical course varied remarkably and could be correlated with the molecular defects. The frequent pathogenic mutations p.R245H, p.Q380R, p.S66W, and c.1080delC were associated with the classical severe phenotype. Patients compound heterozygous for the p.S298P mutation in combination with 1 of the mutations associated with the classical severe phenotype had a significantly longer preservation of psychomotor functions and a longer survival. Two patients homozygous for the p.S298P mutation, and 4 patients from 3 families heterozygous for 3 missense variants not reported previously (p.T421R, p.P180L, and p.L12Q), showed a remarkably attenuated phenotype. INTERPRETATION: We report the natural history and mutational analysis in a large unbiased cohort of MPS IIIA patients. We demonstrate that the clinical spectrum of MPS IIIA is much broader than previously reported. A significant genotype-phenotype correlation was established in this cohort. 01 december 2010 |
| وصف الملف: | application/pdf |
| تدمد: | 1531-8249 0364-5134 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f2a6cab4307795505b06f7a738cda5dTest https://pure.eur.nl/en/publications/c4e808bb-9c46-4f16-b14c-bd400c3109b1Test |
| حقوق: | RESTRICTED |
| رقم الانضمام: | edsair.doi.dedup.....9f2a6cab4307795505b06f7a738cda5d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15318249 03645134 |
|---|