title: Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry.
abstract: Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is an inborn error of the urea cycle. The leading symptom is progressive hyperammonaemia, which is a life-threatening condition, particularly in patients with a neonatal onset. Early diagnosis and treatment of the hyperammonaemia are necessary 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 exchange chromatography in plasma and urine. Here, we report a newborn presenting with coma and severe hyperammonaemia. ASL deficiency was suspected on the basis of an adapted tandem mass spectrometric (MS-MS) procedure which allows determination of argininosuccinate in addition to the amino acids in serum samples. MS-MS measurements revealed a characteristic increase of argininosuccinate, a moderate increase of citrulline, and lowered levels of arginine 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 the argininosuccinate lyase gene. We propose MS-MS as a diagnostic tool suitable for the rapid detection of specific alterations in the amino acid spectra caused by ASL deficiency.
authors.affiliation: Institut für Klinische Chemie, Molekulare Diagnostik und Mitochondriale Genetik, Krankenhaus München-Schwabing, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stadler
authors.forename: K
authors.initials: K
authors.lastname: Gempel
authors.forename: I
authors.initials: I
authors.lastname: Bieger
authors.forename: B F
authors.initials: BF
authors.lastname: Pontz
authors.forename: K D
authors.initials: KD
authors.lastname: Gerbitz
authors.forename: M F
authors.initials: MF
authors.lastname: Bauer
authors.forename: S
authors.initials: S
authors.lastname: Hofmann
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000097:blood; D000641:Ammonia / Q000097:blood; D001120:Arginine / Q000097:blood; D001123:Argininosuccinate Lyase / Q000737:chemistry / Q000235:genetics; D001125:Argininosuccinic Acid / Q000097:blood; D056807:Argininosuccinic Aciduria; D001483:Base Sequence; D002956:Citrulline / Q000097:blood; D003128:Coma / Q000209:etiology; D016368:Frameshift Mutation; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology; D007231:Infant, Newborn; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D015997:Neonatal Screening; D009952:Ornithine / Q000097:blood
chemical_list: D000596:Amino Acids; D001125:Argininosuccinic Acid; D002956:Citrulline; D000641:Ammonia; D001120:Arginine; D009952:Ornithine; D001123:Argininosuccinate Lyase