Nguyen Y, Stirnemann J, Belmatoug N
Service de médecine interne, hôpitaux universitaires Paris Nord-Val-de-Seine, hôpital Beaujon, Assistance publique-Hôpitaux de Paris (AP-HP), 100, boulevard du Général-Leclerc, 92110 Clichy, France; Centre de référence des maladies lysosomales, hôpitaux universitaires Paris Nord-Val-de-Seine, hôpital Beaujon, Assistance publique-Hôpitaux de Paris (AP-HP), 100, boulevard du Général-Leclerc, 92110 Clichy, France.
Centre de référence des maladies lysosomales, hôpitaux universitaires Paris Nord-Val-de-Seine, hôpital Beaujon, Assistance publique-Hôpitaux de Paris (AP-HP), 100, boulevard du Général-Leclerc, 92110 Clichy, France; Service de médecine interne générale, hôpitaux universitaires de Genève, 4, rue Gabrielle-Perret-Gentil, 1211 Genève, Suisse.
Rev Med Interne. 2019 May;40(5):313-322. doi: 10.1016/j.revmed.2018.11.012. Epub 2019 Jan 11.
Gaucher disease is a rare autosomal recessive genetic disease, caused by a deficiency of the lysosomal enzyme, glucocerebrosidase that leads to the accumulation of its substrate (glucosylceramide) in lysosomal macrophages. In the general population, its incidence varies between 0.4 and 5.8/100,000 inhabitants. Type 1 Gaucher disease is the most frequent and is characterized by its extreme heterogeneity including asymptomatic or more severe presentations. The most frequent symptoms are anemia, thrombocytopenia, splenomegaly, and/or hepatomegaly, and a potentially severe bone involvement. Type 2 and type 3 Gaucher diseases are associated with neurological involvement that can be severe. Diagnosis is confirmed by demonstrating a deficiency of glucocerebrosidase activity in leucocytes, and by the identification of biallelic pathogenic variants in GBA1 gene. Type 1 Gaucher disease is associated with a higher risk of Parkinson disease, some solid cancers, and hematologic diseases in particularly multiple myeloma. Specific treatment, such as enzyme replacement therapy or substrate reduction therapy is indicated in symptomatic type 1 Gaucher disease. Only enzyme replacement therapy is indicated in type 3 Gaucher disease. Treatment improves quality of life and prognosis. The rarity of Gaucher disease and its wide variability in clinical presentations lead to diagnosis delays. There is a strong need for a better knowledge of its symptoms among physicians, to reduce irreversible complications.
戈谢病是一种罕见的常染色体隐性遗传病，由溶酶体酶葡糖脑苷脂酶缺乏引起，导致其底物（葡糖神经酰胺）在溶酶体巨噬细胞中蓄积。在一般人群中，其发病率在每10万居民0.4至5.8例之间。1型戈谢病最为常见，其特点是具有极端的异质性，包括无症状或更严重的表现形式。最常见的症状是贫血、血小板减少、脾肿大和/或肝肿大，以及可能严重的骨骼受累。2型和3型戈谢病与可能严重的神经系统受累有关。通过证明白细胞中葡糖脑苷脂酶活性缺乏以及鉴定GBA1基因中的双等位基因致病变异来确诊。1型戈谢病与帕金森病、某些实体癌以及特别是多发性骨髓瘤等血液系统疾病的较高风险相关。有症状的1型戈谢病需采用特异性治疗，如酶替代疗法或底物减少疗法。3型戈谢病仅需酶替代疗法。治疗可改善生活质量和预后。戈谢病的罕见性及其临床表现的广泛变异性导致诊断延迟。迫切需要医生更好地了解其症状，以减少不可逆的并发症。
