Lidove O, Joly D, Barbey F, Blétry O, Grünfeld J P
Service de médecine interne, hôpital Bichat, groupe hospitalier Bichat-Claude Bernard, 46, rue Henri-Huchard, 75018 Paris, France.
Rev Med Interne. 2001 Dec;22 Suppl 3:384s-392s.
Fabry disease is an X-linked recessive abnormality of glycosphingolipid metabolism that is due to deficiency of the lysosomal enzyme alpha-galactosidase A.
A majority of hemizygous men develop severe multisystemic disease (classic form), dominated by renal failure, progressive neurological and cardiac involvement. Nevertheless, some affected men retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female heterozygous carriers are usually asymptomatic; 15% of them, however, have severe involvement of one or several organs. Laboratory, histologic and molecular diagnosis identifies 100% of hemizygous and over 80% of heterozygous subjects.
With developments in molecular genetics, it is now possible to produce the human recombinant enzyme alpha-galactosidase A. Two recent studies had proven that this therapeutic approach was able to be clinically and histologically effective in men. In addition, the results of a trial of gene therapy in a Fabry gene knocked-out mouse appear promising.
法布里病是一种X连锁隐性糖鞘脂代谢异常疾病，由溶酶体酶α-半乳糖苷酶A缺乏所致。
大多数半合子男性会发展为严重的多系统疾病（典型形式），主要表现为肾衰竭、进行性神经和心脏受累。然而，一些患病男性仍保留足够的酶活性，长期无症状（非典型形式）；其主要表现为肥厚型心肌病。女性杂合子携带者通常无症状；然而，其中15%会出现一个或多个器官的严重受累。实验室、组织学和分子诊断可识别出100%的半合子和超过80%的杂合子个体。
随着分子遗传学的发展，现在有可能生产出重组人α-半乳糖苷酶A。最近的两项研究已证明，这种治疗方法在男性中具有临床和组织学疗效。此外，在法布里基因敲除小鼠中进行的基因治疗试验结果看起来很有前景。
