Mignot C, Gelot A, Bessières B, Daffos F, Voyer M, Menez F, Fallet Bianco C, Odent S, Le Duff D, Loget P, Fargier P, Costil J, Josset P, Roume J, Vanier M T, Maire I, Billette de Villemeur T
Neurologie Pédiatrique, Hôpital Armand Trousseau, Paris, France.
Am J Med Genet A. 2003 Jul 30;120A(3):338-44. doi: 10.1002/ajmg.a.20117.
Gaucher disease is a lysosomal storage disease caused by glucocerebrosidase deficiency. Although purely visceral in most cases, some Gaucher disease patients have neurological signs. Signs of Gaucher disease appear after a symptom-free period, except in rare cases with fetal onset. The description of such cases was based mainly on single reports and siblings. We report here a series of perinatal-lethal Gaucher disease cases highlighting the specificity of this phenotype. We retrospectively studied eight original cases of proven Gaucher disease with fetal onset. Non-immune hydrops fetalis was present in all cases but one, and associated with hepatosplenomegaly, ichthyosis, arthrogryposis, and facial dysmorphy. The similarities between our cases and 33 previously described cases allow us to better delineate the perinatal-lethal Gaucher disease phenotype. Hydrops fetalis, in utero fetal death and neonatal distress are prominent features. When hydrops is absent, neurological involvement begins in the first week and leads to death within three months. Hepatosplenomegaly is a major sign, and associated with ichthyosis, arthrogryposis, and facial dysmorphy in some 35-43% of cases. Perinatal-lethal Gaucher disease is a specific entity defined by its particular course and signs that are absent in classical type 2 Gaucher disease. Our study provides clues to the diagnosis of this likely underdiagnosed condition, which must be biochemically confirmed in order to propose appropriate genetic counselling.
戈谢病是一种由葡糖脑苷脂酶缺乏引起的溶酶体贮积病。虽然在大多数情况下仅累及内脏，但一些戈谢病患者有神经系统体征。戈谢病的体征在一段无症状期后出现，胎儿期发病的罕见情况除外。此类病例的描述主要基于个别报告和同胞病例。我们在此报告一系列围产期致死性戈谢病病例，突出了该表型的特异性。我们回顾性研究了8例经证实的胎儿期发病的戈谢病原始病例。除1例病例外，所有病例均出现非免疫性胎儿水肿，并伴有肝脾肿大、鱼鳞病、关节挛缩和面部畸形。我们的病例与之前描述的33例病例之间的相似性使我们能够更好地描述围产期致死性戈谢病的表型。胎儿水肿、宫内胎儿死亡和新生儿窘迫是突出特征。当不存在水肿时，神经系统受累在第一周开始，并在三个月内导致死亡。肝脾肿大是主要体征，约35% - 43%的病例伴有鱼鳞病、关节挛缩和面部畸形。围产期致死性戈谢病是一种特定的疾病实体，由其特殊病程和体征所定义，而这些在经典2型戈谢病中并不存在。我们的研究为诊断这种可能未被充分诊断的疾病提供了线索，必须通过生化检查予以证实，以便提供适当的遗传咨询。
