Byl. Hsu et al., Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome, J PEDIAT, 138(3), 2001, pp. 383-389
Objective: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is a
ssociated with gain of function mutations in the leucine-stimulated insulin
secretion pathway, we examined whether protein feeding or fasting was resp
onsible for hypoglycemia in affected patients.
Study design: Patients with HI/HA (8 children and 6 adults) were studied. A
ll 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 g
gm/kg oral protein tolerance test in 12 patients were compared with respon
ses 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 e
vidence of hyperinsulinism in only 1 of 7 patients. Three did not develop h
ypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated in
appropriate glycemic responses to glucagon that were characteristic of hype
rinsulinism, 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 co
ntrol subjects.
Conclusion: The postprandial blood glucose response to a protein meal is mo
re sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA
syndrome.