Perinatal-lethal Gaucher disease

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.

MeSH terms

  • DNA Mutational Analysis
  • Gaucher Disease / genetics
  • Gaucher Disease / mortality
  • Gaucher Disease / physiopathology*
  • Glucosylceramidase / genetics
  • Glucosylceramidase / metabolism
  • Hepatomegaly / genetics
  • Hepatomegaly / physiopathology
  • Humans
  • Infant
  • Infant, Newborn


  • Glucosylceramidase