Abstract
A subset of patients with type 2 Gaucher disease is characterized by intrauterine onset of rapidly progressive neuropathic disease, arthrogryposis, hydrops fetalis and in some cases restrictive dermopathy. β‐Glucocerebrosidase (β‐glucosidase) activity is usually low or undetectable. In most cases death ensues either in‐utero or within hours or days after birth. We report on an infant born to non‐consanguineous parents of Caucasian origin presenting at birth with hydrops, arthrogryposis, severe respiratory distress, hepatosplenomegaly, and liver failure. Death occurred within several hours after delivery and autopsy revealed typical Gaucher cells in multiple organs in combination with severe apoptotic neurodegeneration throughout the brain. β‐Glucocerebrosidase activity was 1% of the norm in fibroblasts and a novel heterozygous insertion c.1515_1516insAGTGAGGGCAAT was identified by genomic sequencing and an insertion‐specific seminested PCR. In addition, molecular studies revealed a previously described in type 1 Gaucher disease missense mutation c.476G → A which results in a heterozygous substitution of R120Q. Our observations confirm considerable genotypic heterogeneity in patients with type 2 Gaucher disease. The transheterozygous combination of a mutation, previously described in type 1 Gaucher disease, together with a newly identified insertion may result in this severe phenotype. © 2004 Wiley‐Liss, Inc.