Recurrent infantile hypoglycemia due to combined fructose-1,6-diphosphatase deficiency and growth hormone deficiency

Abstract

A 14-month-old female infant presented with recurrent episodes of acute gastroenteritis accompanied by severe metabolic acidosis and hypoglycemia. Physical examination showed hepatomegaly. Laboratory evaluation revealed elevated hepatic enzymes, prolonged prothrombin time, hyperuricemia, and extremely elevated lactate and alanine levels. Glucagon injection during hypoglycemia resulted in a further decrease of blood glucose. She was treated with glucose-containing intravenous fluids, with rapid improvement and normalization of her blood pH and glucose levels. Hormonal assessment during two episodes of hypoglycemia indicated growth hormone (GH) deficiency. However, as isolated GH deficiency could not explain all other concomitant features, such as severe lactic acidosis, hepatomegaly, impaired liver function, and hyperuricemia, the possibility of a combined defect was suggested. Further lymphocytic enzymatic investigation revealed fructose-1,6-diphosphatase deficiency and molecular genetic analysis demonstrated frame shift mutation in the FBP1 gene. This enzyme deficiency causes a rare metabolic disorder not previously described in combination with GH deficiency.

Clinical and Molecular Characterization of Patients with Fructose 1,6-Bisphosphatase Deficiency

“…Laboratory tests usually uncover marked hypoglycemia, lactic acidosis, and elevated levels of uric acid, while liver and kidney functions in most patients have always been reported to be normal [9]. Hypoglycemia-induced insulin drops in insulin and counter-regulatory hormones increase (ACTH, cortisol, and growth hormone) [14]. The attacks decrease with age, and most cases exhibit normal growth and development.…”

Isolated growth hormone deficiency presenting with recurrent hypoglycaemia in a toddler

“…The combination of GHD and another metabolic disorder in the same child as a cause for recurrent hypoglycaemia has also been described. Blumel et al , Takagi et al and Hodax et al described in three separate reports recurrent hypoglycaemia due to a combination of GHD and other metabolic defects (glycogen synthase defect, fructose-1,6-diphosphatase deficiency and glycogen storage disease type IX, respectively) 12–14. On detailed work-up, we could not find any coexisting metabolic defect and hence attribute hypoglycaemia to GHD alone.…”

Fructose‐1,6‐bisphosphatase deficiency causes fatty liver disease and requires long‐term hepatic follow‐up

“…We observed increased prothrombin time in six patients. Some patients have also been reported in the literature with disturbed liver function [11][12][13][14] and Reye's syndrome. 4,15,16 One of these patients presented Reye-like syndrome when he was 20 years old.…”