LONG-TERM MANAGEMENT OF A CASE OF CARBAMYL-PHOSPHATE SYNTHETASE DEFICIENCY USING KETOANALOGS AND HYDROXYANALOGS OF ESSENTIAL AMINO-ACIDS

Abstract

A 13 yr old girl with congenital deficiency of carbamyl phosphate synthetase was treated intermittently for 1 yr with a restricted protein diet supplemented by various mixtures of the .alpha.-ketoanalogs of valine, leucine, isoleucine and phenylalanine; the D,L-.alpha.-hydroxyanalog of methionine; and 5 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 3 exceptions: slightly increased glutamine, pronounced alloisoleucinemia and persistently low phenylalanine. Alloisoleucine was neither incorporated into plasma protein nor excreted in the urine; hence this abnormality was viewed as being clinically insignificant. 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. This therapy provides safe and effective long-term management for this patient''s disorder and may be useful in other cases of congenital hyperammonemia.