Heterogeneous glycogen storage disease in siblings and favorable response to synthetic androgen administration

Abstract

A heterogeneous form of glycogen storage disease is described in two siblings. In the male there was marked deficiency in the liver of glucose-6-phosphatase, but no abnormality of muscle glycogen. In the female there was a moderate diminution of glucose-6-phosphatase activity, associated with deficiency of debranching enzyme in liver and muscle (limit dextrinosis). Both subjects presumably share a deficiency of debranching enzyme in the erythrocyte. The father and a third sibling were found to have twice normal levels of erythrocyte glycogen, suggestive of an effect in the heterozygote. Both children, but particularly the male with glucose-6-phosphatase deficiency, have benefited from the long-term administration of a synthetic androgen, Halotestin. The clinical improvement in the male has been confirmed by laboratory studies, including a normal epinephrine response while receiving this treatment. The possible mechanism of action of this new form of therapy is discussed.