THE CLINICAL, MOLECULAR, AND PATHOLOGICAL CHARACTERIZATION OF A FAMILY WITH 2 CASES OF LETHAL PERINATAL TYPE-2 GAUCHER DISEASE

It has recently been emphasised that a subset of patients with type 2 Gaucher disease die in the neonatal period. This report describes an A fghani family with two conceptuses having severe, prenatally detected Gaucher disease. Mutational analysis showed that the family carried a known complex allele which included mutations at amino acids L444P, A4 56P, and V460V. Although glucocerebrosidase RNA was present, an affect ed fetus had virtually no glucocerebrosidase cross reactive material o n western analyses. The severe clinical course and pathology observed in these patients resemble that of the null allele Gaucher mouse, and suggest that the absence of glucocerebrosidase activity results in ear ly death.