[Metachromatic leucodystrophy. Clinical, biological, and therapeutic aspects].
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.
Barboura
Ilhem
I
Laboratoire de biochimie, CHU Farhat Hached, Sousse, Tunisia. ilhembarboura@yahoo.fr
Ferchichi
Salima
S
Dandana
Azza
A
Jaidane
Zaineb
Z
Ben Khelifa
Souhaira
S
Chahed
Hinda
H
Ben Mansour
Rachida
R
Chebel
Saber
S
Maire
Irène
I
Miled
Abdelhedi
A
D000925:Anticoagulants / Q000627:therapeutic use; D001766:Blindness / Q000209:etiology; D002553:Cerebroside-Sulfatase / Q000172:deficiency*; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics; D005838:Genotype; D006801:Humans; D006868:Hydrolysis; D008607:Intellectual Disability / Q000209:etiology; D007966:Leukodystrophy, Metachromatic / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D009422:Nervous System Diseases / Q000209:etiology; D010641:Phenotype; D013106:Sphingolipidoses / Q000235:genetics; D013107:Sphingolipids / Q000378:metabolism; D013433:Sulfoglycosphingolipids / Q000378:metabolism; D014859:Warfarin / Q000627:therapeutic use; D001617:beta-Glucosidase / Q000172:deficiency
D000925:Anticoagulants; D013107:Sphingolipids; D013433:Sulfoglycosphingolipids; D014859:Warfarin; D002553:Cerebroside-Sulfatase; D001617:beta-Glucosidase