​A four-day-old boy with a positive result in newborn-screening testing was referred to the hospital for further evaluation. He was the product of a 39-week gestation and appeared well at birth. His laboratory results included the following plasma findings: ammonia, 109 μg/dL (reference interval, 20–65 μg/dL); citrulline, 169 μmol/L (reference interval, 2–50 μmol/L); and leucine, 278 μmol/L (reference interval, 32–153 μmol/L). Also found were increases in homocysteine and γ-aminobutyric acid. The amino acid spectrum is shown below (Fig. 1). 

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Fig. 1. Amino acid spectrum for the patient.

The patient's plasma sample was analyzed on a Hitachi L-8800 amino acid analyzer after removing proteins by treatment with 40 g/L sulfosalicylic acid/internal standard solution, centrifugation, and filtration. The amino acids were separated by high-resolution ion-exchange chromatography and then subjected to postcolumn ninhydrin derivatization; detection was by spectrophotometry at 570 nm and 440 nm. The areas under the curves were calculated by using the manufacturer's software for final quantification. Hcys, homocysteine; γ-ABA, γ-aminobutyric acid; AEC, S-2-aminoethyl-l-cysteine; 3-M Histidine, 3-methylhistidine. 

Questions

  1. What class of genetic disorders did this patient most likely have?
  2. What enzyme deficiency was suggested by the patient's amino acid profile, and how did you reach the conclusion?
Read the article here for the answers.