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


METHODS
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.


CONCLUSIONS
The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome.
Hsu
B Y
BY
Division of Endocrinology, the Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Kelly
A
A
Thornton
P S
PS
Greenberg
C R
CR
Dilling
L A
LA
Stanley
C A
CA
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004044:Dietary Proteins / Q000009:adverse effects*; D005215:Fasting / Q000009:adverse effects*; D005260:Female; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000235:genetics / Q000503:physiopathology*; D006946:Hyperinsulinism / Q000235:genetics / Q000503:physiopathology*; D007003:Hypoglycemia / Q000209:etiology*; D007223:Infant; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D013577:Syndrome
D004044:Dietary Proteins; D005969:Glutamate Dehydrogenase