Gaucher Disease: Clinical, Biological and Therapeutic Aspects.

We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme ß-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.

[MODY type diabetes: overview and recent findings]. / Le diabète de type MODY: revue générale et récentes découvertes.

We present an update of knowledge on diabetes MODY (maturity onset diabetes of the young), including the recent molecular discoveries, and new diagnostic strategies. Considerable progress has been made in understanding the different molecular abnormalities that cause MODY and the phenotypic consequences resulting therefrom. MODY diabetes is very heterogeneous and is the most common form of monogenic diabetes. Its distribution is worldwide. MODY is an autosomal dominant diabetes mellitus, nonketotic and occurs at an early age (usually before 25 years). To date, at least seven genes are associated with MODY, with frequencies that differ from one population to another. Both 2 and 3 subtypes predominate, while other subtypes (1, 4, 5, 6 and 7) concern only a few families. Since its discovery in the sixties, studies have succeeded to fully clarify the epidemiological, molecular and clinical diagnosis of each subtype, to provide better care for patients. However, the subject of MODY has not yet revealed all its secrets. Indeed, it remains to identify other genes that are associated with MODY X.

[Metachromatic leucodystrophy. Clinical, biological, and therapeutic aspects]. / La leucodystrophie métachromatique Aspects clinique, biologique et thérapeutique.

Scholz's disease or metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency in arylsulfatase A (ARSA: EC 3.1.6.8). This enzyme is responsible for the degradation of sulfatides commonly called cerebroside-3-sulfate or 3-O-sulfogalactosylcéramide in galactocérébroside and sulfate. The success of hydrolysis of these sphingolipids by ARSA necessarily depends on the presence of saposine B forms a complex with the substrate. The pathological accumulation of sulfatides in the nervous system (myelin, neurons and glial cells) results most often neurological, mental retardation, nervous disorders, blindness. The metachromatic granules accumulated in the central nervous system and peripheral compounds are highly toxic. These are at high levels in the urine of patients affected by the MLD. Arylsulfatase A activity is collapsed in these patients. Unfortunately, the value of enzyme activity is not a predictor of clinical severity of the neuropathology. In contrast, the study of the gene that codes for the ARSA is seen as a way to diagnose the simplest and most reliable of the disease to avoid misdiagnosis due to the presence of pseudodeficit. The conventional therapeutic approaches are essentially symptomatic. They were made in order to restore the enzyme activity of arylsulfatase A and prevent the progression of the pathological accumulation of sulfatides and consequently reduce morbidity associated with MLD.