[Fabry disease in 2004].
Fabry disease is a hereditary metabolic disease, with an X-linked transmission, that is due to the deficit of alpha-galactosidase A, a lysosomal enzyme. The enzyme deficiency is responsible for an accumulation of neutral glycosphingolipids in the organism with a consequent disease of overload that is responsible for pain, dermatological, renal, cardiac, gastro-intestinal, cochlear and neurological manifestations. Fabry disease starts during childhood but the diagnosis is often made too late. An early diagnosis is nevertheless essential in order to commence a treatment before the occurrence of morbid cardio or cerebro-vascular accidents, or the development of end-stage chronic renal failure. Some phenotypic variants of Fabry disease are probably under-diagnosed among patients with so-called idiopathic hypertrophic cardiomyopathy on haemodialysis. Treatment by substitution of the enzyme with a recombinant alpha-galactosidase has been recently validated in breakthrough controlled clinical trials. Substitutive enzyme treatment represents a major therapeutic development. At the same time, it raises numerous questions such as the ideal age for initiation of treatment, the dose and the optimal frequency of enzyme administration, the reversibility of certain histopathological lesions and the determination of the best markers for the assessment and follow-up of the efficacy of treatment. Monitoring of the plasma levels of the enzyme substrate and the antibody titre seem to be essential. The documentation of short-term clinical benefits could require the use of sophisticated investigation methods such as the study of the myocardial function by tissue Doppler imaging.
Germain
Dominique-Paul
DP
Unit de génétique clinique, Hôpital européen Georges Pompidou, 75015 Paris. dominique.germain@hop.egp.ap-hop-paris.fr
D000367:Age Factors; D002648:Child; D017326:Clinical Trials, Phase III as Topic; D004311:Double-Blind Method; D000795:Fabry Disease / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007527:Isoenzymes / Q000008:administration & dosage / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D015337:Multicenter Studies as Topic; D010641:Phenotype; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000627:therapeutic use
D007527:Isoenzymes; D010919:Placebos; D000519:alpha-Galactosidase; C459420:agalsidase beta