The present clinical conference takes up the case of a 5½-month-old boy who was admitted to the hospital because of irritability and failure to gain weight. His irritability progressed to definite neurologic signs, and marked enlargement of the spleen developed, together with some hepatomegaly. Bone marrow aspiration revealed abnormal cells, showing an eccentric nucleus and wavy, fibrillar cytoplasm, with an appearance consistent with Gaucher cells. A progressively downhill course ensued, characterized by opisthotonus and respiratory difficulties, and the child died at age 7 months.
A discussion of numerous aspects of Gaucher's disease is presented, including biochemical and genetic considerations. The problems encountered in genetic counseling of parents who have children with this disease are brought out. Since Gaucher's disease as a syndrome exhibits a heterogenous pattern of inheritance, the dangers inherent in giving parents oversimplified genetic data are emphasized. If the parents ebect to have no further children of their own and instead wish to adopt children, certain implications which this course of action may raise are discussed.
An experiment is described wherein spleen tissue obtained from two patients with Gaucher's disease was analyzed for cerebroside content. Most of the cerebroside found in both spleens was the abnormal glucose form, whereas in normal human tissue the galactose cerebroside predominates. Studies are being made in this laboratory of the incorporation of carbon-14 labelled glucose and galactose using microsomal fractions of spleens from patients with Gaucher's disease. On the basis of preliminary data, it is postulated that the site of the biochemical error in most patients with the disease is at the conversion of the glucocerebroside to the galactocerebroside. It is believed that a defect in a UDP-galactose-4-epimerase-like mechanism at this site would cause the accumulation of the "abnormal" glucose cerebroside. Figure 5 indicates graphically the location of this suggested metabolic block.