A 6-month-old boy was admitted with failure to thrive. Laboratory tests showed hypoglycemia and high glutamine and uracil levels in urine. Gastric tube feeding was not tolerated. The child became comatose and then parenteral dextrose was given. The child recovered from coma within 24 hrs. Which of the following enzyme is defective?
From the given clinical and laboratory data, the diagnosis is hyperammonemia type 2, which is due to the deficiency of the enzyme ornithine transcarbamoylase. There is an accumulation of carbamoyl phosphate, which then enters into pyrimidine synthesis producing orotic acid and uracil and leading to orotic aciduria and high uracil in blood and urine. High glutamine: Since the ammonia from glutamine is not conveed into urea, its level raises. Hypoglycemia: Since glutamate is not available for transamination, amino acids cannot be used for gluconeogenesis. Treatment: Limiting intake of ammonia and increasing its excretion. Dietary protein, a metabolic source of ammonium, is restricted and caloric intake is provided by glucose and fat. Addition of Phenylbutyrate which scavenges nitrogen by combining with amino acids to form a more water-soluble product, which can be easily excreted by the kidneys. Reference: Harpers illustrated biochemistry 30th edition
Argininosuccinate synthase
Carbamoyl phosphate synthase I
Argininosuccinate lyase
Ornithine transcarbamoylase
Metabolism of protein and amino acid