Long-term management of a case of carbamyl phosphate synthetase deficiency using ketanalogues and hydroxyanalogues of essential amino acids.

A 13-year-old girl with congenital deficiency of carbamyl phosphate synthetase has been treated intermittently for one year with a restricted protein diet supplemented by various mixtures of the alpha-ketoanalogues of valine, leucine, isoleucine, and phenylalanine, the D,L-alpha-hydroxyanalogue of methionine, and five amino acids (lysine, arginine, histidine, threonine and tryptophan). Numerous adjustments in the composition of this mixture were made. Eventually normal levels of plasma ammonia and most amino acids were achieved, with three exceptions: slightly increased glutamine, pronounced alloisoleucinemia, and persistently low phenylalanine. Alloisoleucine was shown not to be incorporated into plasma protein and not to be excreted in the urine; hence this abnormality was viewed as being clinically insiginificant. Hypophenylalaninemia was unexplained, and failed to respond to increased phenylpyruvate dosage or phenylalanine itself; renal clearance of phenylalanine was high but could not account for the low plasma level. Compared to the pretreatment period her clinical status has improved markedly. Physical and mental development has continued at the same rate. Temporary withdrawal of the supplements led to prompt increases in plasma ammonia, glutamine, and alanine. We conclude that this therapy provides safe and effective long-term management for this patient's disorder and may be useful in other cases of congenital hyperammonemia.