EARLY TREATMENT OF COMPLETE ORNITHINE TRANSCARBAMYLASE DEFICIENCY WITH KETO ANALOGUES OF ESSENTIAL AMINO ACIDS

Abstract

Complete deficiency of the urea cycle enzyme, ornithine trans-carbamylase (OTC), causes hyperammonemia and death in the neonatal period. Past therapeutic attempts have been singularly unrewarding. We now report treatment of such a male infant (hepatic OTC activity 0.1% of control) from the second day of life with a dietary regimen in which a mixture of essential amino acids and their nitrogen free analogues supplements a protein-restricted milk-based formula. Milk protein (1 g/kg/d) is supplied by standard infant formula and caloric needs (130 Cal/kg/d) and trace elements by a synthetic, protein-free product. To this formula is added a mix consisting of threonine, histidine, lysine, tryptophan, and arginine, plus the keto analogues of valine, leucine, isoleucine and the hydroxy analogues of methionine and phenylalanine, each in a quantity exceeding the infant's daily requirements. On this regimen the child has grown normally to the present time (age 9 wks) and his blood ammonia concentrations are persistently within normal limits (<150 μg/dl). Balance studies have shown normal nitrogen retention for age and intake. Plasma amino acid concentrations are near normal with the exception of reduced values for the branched chain amino acids and arginine which necessitated dietary adjustment at age 6 wks. To our knowledge this child now has lived longer than any previously reported infant with OTC deficiency of this severity.