The effects of
growth hormone treatment and dietary
alanine supplementation, individually and in combination, were studied in five patients with organic acidemias. Three patients had
propionic acidemia, one had 3-hydroxyisobutyric acidemia, and one had a defect in
isoleucine metabolism. Two patients with
propionic acidemia had decreased
growth hormone secretion in response to provocative stimuli (intravenous
L-arginine and oral
levodopa or
clonidine); the remaining subjects had sufficient
growth hormone secretion. Three of four subjects in whom IGF1 was measured showed subnormal concentrations at baseline (including two with normal
growth hormone secretory responses). All patients showed an increase in linear growth with
growth hormone. In the four patients studied, all had a significant increase in
nitrogen retention over baseline with
alanine or
growth hormone alone, or with the combination of
growth hormone and
alanine, with a much greater effect of
growth hormone. Lean body mass and body fat composition tended to become normal with treatment.
Protein tolerance increased, and when the patients'
dietary protein intakes were increased between 20 and 60% they maintained positive
nitrogen balance, without a significant increase in metabolite excretion. One patient with
propionic acidemia expired during the time of the study, following a course of recurrent
pancreatitis and an episode of acute basal ganglia
infarction. All of the other subjects showed clinical improvement (decreased incidence of ketoacidotic episodes and decreased frequency of hospital admission and school absence) during treatment, and even the patient who expired remained metabolically stable up to and through the terminal event. We conclude that
growth hormone may be of value in the management of patients with organic acidemia.