EPIDERMAL ABNORMALITIES MAY DISTINGUISH TYPE-2 FROM TYPE-1 AND TYPE-3OF GAUCHER DISEASE

A major clinical challenge in Gaucher disease is the early and presymp tomatic discrimination of type 2 (acute neuronopathic) from milder typ e I and type 3 Gaucher patients to enable appropriate management and c ounseling, Although most patients with Gaucher disease do not have ski n abnormalities, a subset of patients with severe type 2 Gaucher disea se display ichthyosiform skin. Analogous findings occur in the skin of type 2 (null allele) Gaucher mice. Ultrastructural and functional stu dies of epidermis from these mice reveal that glucocerebrosidase is re quired to generate functionally competent membranes for normal epiderm al barrier function, We have extended our studies by examining the epi dermal lipid content and ultrastructure in all three types of Gaucher patients. Only the type 2 Gaucher patients, some of whom had clinical ichthyosis, demonstrated an increased ratio of epidermal glucosylceram ide to ceramide as well as extensive ultrastructural abnormalities, in cluding the persistence of incompletely processed lamellar body-derive d contents throughout the stratum corneum interstices. These epidermal alterations may provide a means for early differentiation of type 2 G aucher disease.