Fructose-1,6-diphosphatase deficiency, hypoglycemia, and response to folate therapy in a mother and her daughter

Abstract Symptomatic fasting and reactive hypoglycemia in association with low iejunal and hepatic fructose-1,6-diphosphatase (FDPase) activity were found in an adult patient and her 19-month-old daughter. Plasma glucose response to glycerol ingestion was abnormal in both, showing little change in the adult and a decline in the child. FDPase activity was low in tissues from both patients. This reduced enzyme activity defines a new variant of the fructose-1,6-dipphosphatase deficiency state(s) which is mild in its manifestations and thus more resistant to the hypoglycemia-provoking effects of fructose and alanine. No difference was detected between the FDPase from these patients and unaffected individuals by polyacrylamide gel electrophoresis. The K m of the jejunal enzyme for fructose diphosphate in the adult was similar to the normal control. Glucagon rapidly increased the activity of hepatic FDPase in both patients. Folic acid, 15 mg/day, increased hepatic and jejunal FDPase activity in both patients. After folate therapy, there was improvement in the adult's symptoms and improvement in the child's ability to maintain normal plasma glucose levels. The interrelationship between the hypoglycemia, FDPase deficiency, and the response to folate therapy was discussed.