"Ketotic Hypoglycemia" Due to Hepatic Fructose-1,6-Diphosphatase Deficiency

A 2½-year-old girl who fulfilled certain of the diagnostic criteria of ketotic hypoglycemia was found to have intolerance to glycerol and fructose. Intestinal and hepatic biopsy tissues were assayed for pyruvate kinase, fructose-1-phosphate aldolase, fructose-1,6-diphosphate aldolase, and fructose-1,6-diphosphatase (FDPase) activities. All enzyme activities were normal except FDPase which was less than normal in both tissues. Since pharmacologic doses of folic acid cause an increase in jejunal and hepatic FDPase, the patient was treated with 30 mg of folic acid per day. Hepatic FDPase activity increased by 60% and tolerance to glycerol, fructose, and alanine improved. Hypoglycemia no longer occurred with the ketosis produced by a ketogenic diet.