[Mucopolysaccharidosis type I in Morocco: clinical features and genetic profile]. / Mucopolysaccharidose de type I au Maroc: manifestations cliniques et profil génétique.

BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders due to lysosomal enzyme deficiencies, leading to glycosaminoglycan accumulation in lysosomes of different tissues. The aim of this study was to characterize MPS types, particularly MPS I, which are difficult to differentiate by clinical features. PATIENTS AND METHODS: Over a period of three years (June 1996-May 1999), 16 Moroccan patients (3-20 years old) with MPS were investigated. Twelve of them came from the Souss region. In subjects with suspected clinical MPS I or II, the diagnosis was confirmed by biochemical investigations, which included the quantification of total glycosaminoglycans (GAGs) released in urine, their identification, and the assay of alpha-L-iduronidase activity in leucocytes. A molecular analysis was performed in parallel, to provide the genetic proof of the diagnosis. RESULTS: These 16 patients belonged to 12 families, nine of which were consanguineous (75%). Twelve patients had Hurler syndrome and three had Hurler/Scheie's syndrome; no case of Scheie's syndrome was observed. Short stature, coarse face, organomegaly, hernia, cardiac disease, mental delay and dysostosis were observed in variable degrees. We report three cases without corneal clouding. Increased total urinary GAGs, identified as dermatan sulfate and heparan sulfate by thin-layer chromatography and total deficiency of alpha-L-iduronidase activity, were noted in studied subjects. At the molecular level the P533R mutation was detected in 24 among 26 alleles studied. CONCLUSION: It is now possible to perform the screening of MPS I and II in Morocco by analysis of clinical, radiologic observations and biological investigation. The predominance of P533R mutation could permit the screening of healthy heterozygotes and genetic counselling for families of Moroccan descent.

Mucopolysaccharidosis type I: characterization of a common mutation that causes Hurler syndrome in Moroccan subjects.

A group of 13 Moroccan patients with MPS I and their families, including three siblings and twin siblings, was screened for mutations of the alpha-L-iduronidase gene using fluorescence-assisted mismatch analysis (FAMA) and cycle sequencing of PCR products. The P533R mutation, which is rare in Europeans, was identified in 92% of mutant alleles (24/26). This is the highest frequency of this mutation detected in patients with Hurler syndrome. None of the patients carried the W402X or Q70X alleles, the most common MPS I mutations in Europeans. These results suggest that the P533R mutation constitutes the genetic lesion which results in MPS I in people of Moroccan descent and provides yet more evidence for the uneven geographical distribution of mutations in MPS I.