Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome

J Pediatr. 2001 Mar;138(3):383-9. doi: 10.1067/mpd.2001.111818.


Objective: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for hypoglycemia in affected patients.

Study design: Patients with HI/HA (8 children and 6 adults) were studied. All had dominantly expressed mutations of glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The responses to a 24-hour fasting test were determined in 7 patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients were compared with responses of 5 control subjects.

Results: The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with HI/HA showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with HI/HA and control subjects.

Conclusion: The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Dietary Proteins / adverse effects*
  • Fasting / adverse effects*
  • Female
  • Glutamate Dehydrogenase / genetics
  • Glutamate Dehydrogenase / metabolism
  • Humans
  • Hyperammonemia / genetics
  • Hyperammonemia / physiopathology*
  • Hyperinsulinism / genetics
  • Hyperinsulinism / physiopathology*
  • Hypoglycemia / etiology*
  • Infant
  • Male
  • Middle Aged
  • Postprandial Period
  • Syndrome


  • Dietary Proteins
  • Glutamate Dehydrogenase