title: Rapid diagnosis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency via enzyme activity measurements in leukocytes or platelets using a simple spectrophotometric method.
abstract: Patients with 3-hydroxy-3-methylglutaric aciduria due to a deficiency of 3-hydroxy-3-methylglutaryl Coenzyme A lyase usually present with a life-threatening crisis of hypoglycemia, metabolic acidosis and hyperammonemia. Diagnosis of this inborn error of leucine degradation is usually based upon gas-chromatographic analysis of organic acids in a patient's urine. In this paper we describe a simple spectrophotometric method allowing the activity of HMG-CoA lyase to be measured in leukocytes or platelets within a few hours, thus contributing to a rapid, unequivocal diagnosis and subsequent treatment. The validity of the method was established by demonstrating a deficient activity of HMG-CoA lyase in two patients with 3-hydroxy-3-methylglutaric aciduria. Furthermore, using this method, heterozygote detection can be done with great reliability.
authors.affiliation: Department of Pediatrics, University Hospital Amsterdam, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: P H
authors.initials: PH
authors.lastname: Zoeters
authors.forename: R B
authors.initials: RB
authors.lastname: Schutgens
authors.forename: J B
authors.initials: JB
authors.lastname: de Klerk
authors.forename: M
authors.initials: M
authors.lastname: Duran
authors.forename: S K
authors.initials: SK
authors.lastname: Wadman
authors.forename: F J
authors.initials: FJ
authors.lastname: van Sprang
authors.forename: A M
authors.initials: AM
authors.lastname: Hemmes
authors.forename: B S
authors.initials: BS
authors.lastname: Voorbrood
mesh_terms: D001792:Blood Platelets / Q000201:enzymology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007223:Infant; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis; D007652:Oxo-Acid-Lyases / Q000097:blood / Q000172:deficiency*; D013053:Spectrophotometry / Q000379:methods
chemical_list: D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase