Pathogenesis of maple-syrup-urine disease: observations during dietary management and treatment of coma by peritoneal dialysis

Abstract

Experiences with the management of a case of maple-syrup-urine disease from early infancy to death at 18 months of age are summarized. The use of a mixture of l-amino acids as the basis of a diet restricted in the branched-chain amino acids allowed the inclusion of a maximal amount of natural protein as the source of the essential branched-chain amino acids. The apparent importance of this natural source of the branched-chain amino acids for normal growth is emphasized. Myelination of the brain was normal on histological examination. The use of peritoneal dialysis for the treatment of coma which had not responded to vigorous intravenous therapy is discussed. Clear-cut neurological improvement occurred during dialysis without concomitant improvement in the metabolic acidosis. The branched-chain amino acids and their oxo acids did not account for the large negative base excess. Of plasma amino acids, mainly the branched-chain amino acids appeared in the dialyzate, with only modest decreases in the plasma levels. Thus, the plasma pool of branched-chain amino acids was being continously replenished by a large intracellular pool. A similar episode of coma occurring at 18 months of age was not so treated, and ended in death. The dramatic clinical and electroencephalographic response during dialysis and the apparently complete recovery which followed suggests that a diffusible “toxic” factor may be responsible for the coma of maple-syrup-urine disease, but does not itself establish that the branched-chain amino acids or their oxo acids are the etiological agents. The “toxic” factor may have little if anything to do with permanent structural changes and may result in coma and seizures in a brain that is apparently normal histologically. Further evaluation of these therapcutic approaches is warranted, but these exiguous results do not permit unbridled optimism.