title: GC/MS analysis of urine in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
abstract: A patient with 3-hydroxy-3-methylglutaric aciduria was diagnosed using gas chromatography mass spectrometry. The patient had severe metabolic acidosis, hypoglycemia and hyperammonemia and excreted abnormal amounts of 3-methylglutaconic, 3-hydroxy-3-methylglutaric, 3-methylglutaric, 3-hydroxyisovaleric and glutaric acids in the urine. 3-Hydroxy-3-methylglutaric acid appeared as two peaks on the chromatogram after trimethylsilylation. One was a tri-trimethylsilyl and the other a di-trimethylsilyl derivative. 3-Methylglutaconic acid appeared as three peaks: cis-, trans- and cyclic cis-isomers. The structure of these derivatives was elucidated by deuterium-labeled trimethylsilyl derivatization. The di-trimethylsilyl derivative of 3-hydroxy-3-methylglutaric acid and the cyclic cis-isomer of 3-methylglutaconic acid do not appear to have been previously described. After treatment with leucine restriction milk, the excretion of leucine catabolites decreased but 3-methylglutaconic and 3-hydroxy-3-methylglutaric acids continued to be excreted at abnormally high levels. It is concluded that these two metabolites are necessary for the chemical diagnosis of HMG-CoA lyase deficiency. This patient is the first case of HMG-CoA lyase deficiency to be reported in Japan.
authors.affiliation: Division of Human Genetics, Kanazawa Medical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shinka
authors.forename: T
authors.initials: T
authors.lastname: Kuhara
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: I
authors.initials: I
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Irimichi
authors.forename: K
authors.initials: K
authors.lastname: Hasumi
authors.forename: A
authors.initials: A
authors.lastname: Endo
mesh_terms: D000138:Acidosis / Q000235:genetics / Q000378:metabolism; D002849:Chromatography, Gas; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007231:Infant, Newborn; D016350:Leucine Zippers / Q000276:immunology; D013058:Mass Spectrometry; D015093:Meglutol / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D008661:Metabolism, Inborn Errors; D007652:Oxo-Acid-Lyases / Q000172:deficiency* / Q000378:metabolism / Q000652:urine; D014297:Trimethylsilyl Compounds / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D014297:Trimethylsilyl Compounds; D015093:Meglutol; D007652:Oxo-Acid-Lyases