Treatment of the acute crisis in maple syrup urine disease.
BACKGROUND
The acute crisis of metabolic decompensation in maple syrup urine disease is a potentially lethal medical emergency that requires reduction in concentrations of leucine and other branched-chain amino acids in plasma. Experience with intravenous mixtures of amino acids indicates that this can be accomplished by the synthetic forces of protein synthesis. However, these intravenous mixtures are not generally available.


OBJECTIVE
To develop enteral mixtures suitable for administration by nasogastric drip in minimal volume.


METHODS
Mixtures of amino acids were designed containing no leucine, isoleucine, or valine for administration by nasogastric drip. Needs for water and calories were to be met intravenously. They were designed to be used in the management of the acute crisis.


METHODS
Inpatient pediatric service.


METHODS
Two patients with maple syrup urine disease. Data were collected during the management of 3 episodes of metabolic imbalance.


METHODS
Studies were carried out for 4 to 11 days, during which there was no intake of leucine. Four different mixtures were used and a fifth was designed on the basis of this experience.


METHODS
Effects on the concentrations of leucine and the other branched-chain amino acids. Clinical status closely mirrored the concentration of leucine.


RESULTS
In each instance, a progressive fall in leucine concentration was obtained. Rates of fall were comparable to those obtained with intravenous therapy. Concentrations of isoleucine fell to levels that made this amino acid limiting for protein synthesis and hence therapeutic effect. This led to greater and earlier supplementation with isoleucine. Valine supplementation was also useful.


CONCLUSIONS
The acute crisis of metabolic imbalance in maple syrup urine disease may be effectively treated by the continuous intragastric drip of solutions of amino acids devoid of leucine along with provision of water and calories intravenously.
Nyhan
W L
WL
Department of Pediatrics and Institute for Molecular Genetics, University of California San Diego, La Jolla 92093-0830, USA.
Rice-Kelts
M
M
Klein
J
J
Barshop
B A
BA
D000208:Acute Disease; D000596:Amino Acids / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007441:Intubation, Gastrointestinal; D007930:Leucine / Q000097:blood / Q000652:urine; D008297:Male; D008375:Maple Syrup Urine Disease / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000596:Amino Acids; D007930:Leucine