Rapid diagnosis of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency via enzyme activity measurements in leukocytes or platelets using a simple spectrophotometric method.
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.
Wanders
R J
RJ
Department of Pediatrics, University Hospital Amsterdam, The Netherlands.
Zoeters
P H
PH
Schutgens
R B
RB
de Klerk
J B
JB
Duran
M
M
Wadman
S K
SK
van Sprang
F J
FJ
Hemmes
A M
AM
Voorbrood
B S
BS
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
D007652:Oxo-Acid-Lyases; C021410:3-hydroxy-3-methylglutaryl-coenzyme A lyase