Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry

Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is an inborn err or of the urea cycle. The leading symptom is progressive hyperammonaemia, w hich is a life-threatening condition, particularly in patients with a neona tal onset. Early diagnosis and treatment of the hyperammonaemia are necessa ry to improve survival and the long-term outcome of ASL-deficient patients. Currently, the diagnosis of ASL deficiency is based on the measurement of urea cycle intermediates and amino acids by automated quantitative ion exch ange chromatography in plasma and urine. Here, we report a newborn presenti ng with coma and severe hyperammonaemia. ASL deficiency was suspected on th e basis of an adapted tandem mass spectrometric (MS-MS) procedure which all ows determination of argininosuccinate in addition to the amino acids in se rum samples. MS-MS measurements revealed a characteristic increase of argin inosuccinate, a moderate increase of citrulline, and lowered levels of argi nine and ornithine in the serum of the patient. The diagnosis was confirmed by the detection of a novel homozygous frameshift mutation in exon 14 of t he argininosuccinate lyase gene. We propose MS-MS as a diagnostic tool suit able for the rapid detection of specific alterations in the amino acid spec tra caused by ASL deficiency.