[Mucopolysaccharidosis type I: identification of alpha-L-iduronidase mutations in Tunisian families]. / La mucopolysaccharidose de type I: identification des mutations du gène alpha-L-iduronidase dans des familles tunisiennes.

UNLABELLED: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease due to mutations in the gene encoding alpha-l-iduronidase (IDUA) leading to variable clinical phenotypes with progressive severe organomegaly, bone and neurological involvement in the most severe forms. The aim of our study was to propose in Tunisia a strategy of molecular and prenatal diagnosis of the MPS I. POPULATION AND METHODS: Our study was carried out on 8 MPS I patients recruited from different Tunisian regions and issued from 5 unrelated families. All the patients were offspring of consanguineous marriages. RESULTS: The clinical and biological study led to diagnose 5 Hurler patients and 3 Hurler-Scheie patients. Three IDUA mutations were identified by molecular analysis within 6 different families: a novel mutation p.F602X and 2 already described mutations p.P533R and p.R628X. DISCUSSION: MPS I is a heterogeneous disease characterized by variability of the phenotypes. The missense mutation p.P533R associated with the intermediate phenotype was the most frequent in the Tunisian but also in the Moroccan population. In Tunisia, the incidence of p.P533R mutation seems to be associated with the high frequency of consanguineous marriages. CONCLUSION: The identification of known MPS I mutations (p.P533R and p.R628X) and of the novel mutation p.F602X permits reliable genetic counselling of at-risk relatives and molecular prenatal diagnosis.

[Clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients]. / Etude de la maladie de Morquio A dans une famille tunisienne présentant deux enfants atteints.

Mucopolysaccharidosis type IV A (MPS IV A) is an autosomal recessive disorder resulting from the deficient activity of the lysosomal enzyme, N-acetylgalactosamine-6-sulfate sulfatase (GALNS) and the progressive lysosomal accumulation of keratane sulfate. Clinically, the MPS IV A differs from the other MPS by the localisation of the keratane sulfate in skelet and in eyes associated to the conservation of a normal intelligence. To date, the characterization and purification of the GALNS gene made a research for pathogenic mutations in patients with MPS IV A easier. These mutations are responsible of severe, intermediate or mild phenotype. The aim for this work was the research of clinical, biologic and molecular characteristics of two Tunisian MPS IV A patients who were offsprings of consanguineous mating. Enzymatic and urinary diagnostics suggested a MPS IV A phenotype. A novel homozygous mutation IVS1+1G-A was identified by direct sequencing in the GALNS gene of the two patients. Identification of GALNS mutations provide genotype/phenotype correlations and permit the precision of anomalies responsible of Morquio A phenotype in concerned families.

[Imerslund-Najman-Grasbeck anemia. Apropos of a case]. / L'anémie d'Imerslund-Najman-Grasbeck. A propos d'un cas.

Imerslund-Najman-Grasbeck disease is a rare inherited megaloblastic anaemia secondary to a selective malabsorption of vitamin B12 by ileal enterocytes. The authors report on a 4 year-old tunisian girl who presented as visceral infantile leishmaniasis because of huge splenomegaly and major anaemia. The diagnosis of Imerslund disease was performed on the basis of the association of typical megaloblastic cells in the marrow, permanent proteinuria and favourable outcome under parenteral B12 administration. In addition, ther were no folate deficiency, no anti-intrinsic factor antibodies and no intrinsic factor deficiency. The outcome of the disease is always favourable if parenteral administration of vitamin B12 maintained.