A New Glucose-6-Phosphate Dehydrogenase Deficient Variant in a Patient With Chediak-Higashi Syndrome

Abstract

A description is given of enzymatic characteristics of a new glucose-6-phosphate dehydrogenase variant (G-6-PD) found in 2 male members of an inbred Pakistani family. Properties of this enzyme differ in respect to electrophoretic mobility, utilization of deamino NADP, and Km for both G-6-PD and NADP from the variant reported to be common in Pakistan. The propositus, in addition to G-6-PD deficiency, also had Chediak-Higashi syndrome. Some male members of this family are affected by two distinct clinical disorders. One disease is characterized by intermittent jaundice and anemia, often concurrent with infection, compatible with G-6-PD deficiency. The other is characterized by severe, frequent, and occasionally fatal infections that are not necessarily associated with jaundice, a disease pattern compatible with Chediak-Higashi syndrome. A possible additive relationship of G-6-PD deficiency with Chediak-Higashi syndrome in causing frequent infections was examined. Only moderately decreased activity of G-6-PD was found in nonerythroid cells of 2 male children having this G-6-PD deficient variant. Moreover, the study of the patient's mother revealed no obvious survival disadvantage of her nonerythroid cell clones carrying the G-6-PD-deficient variant as compared to the clones carrying the normal G-6-PD isoenzyme. Ascorbic acid therapy for the brother affected by both of these diseases did not lead to increased hemolysis. No obvious clinical improvement of severity and infection frequency was noted after several months of ascorbic acid therapy.