Korean J Clin Pathol.  1997 Dec;17(6):1022-1028.

Quantitation of Methylmalonic Acid by Isotope Dilution Gas Chromatography Mass Spectrometry

• Kim JU
• Kim JW

Abstract

BACKGROUND: Methylmalonic aciduria can be caused by inherited defects in the methylmalonyl-CoA mutase enzyme, Inherited defects in the metabolism of vitamin Bl2 and acquired or inherited vitamin Bl2 deficiency. Quantitation of urinary methylmalonic acid (MMA) is very useful In diagnosis of methylmalonic acidemia and cobalamin deficiency. We evaluated a quantitation method of urinary MMA and determined reference values.
METHODS
The method involved stable isotope dilution gas chromatographymass spectrometry (GC-MS) with (methyl 2H3)-MMA as the internal standard. We determined the detection limit, linearity and periodic variations of the assay. Urinary MMA levels were measured in 70 individuals of ages newborn to 58 years with no metabolic disorders.
RESULTS
The lower limit of detection calculated from blank runs (mean+/-3SD) was 2.62nmo1/m1. One control urine tramp)e analyzed 23 times within 3 weeks game results of 7.83+/-1.09 (mean+/-SD, CV=13.8%) nmol/mL. The linearity at four different concentrations of MMA was acceptable (R2=0.9992). The concentration of urinary MMA in 70 individuals was 2.33+/-2.19 mmol/mol creatinine (mean+/-SD). Age related reference values which decreased with age were also reported (p=1.23x10-9).
CONCLUSIONS
The described method is sensitive, specific and noninvasive, which is considered the gold standard method for measuring MMA. The method could be used as a screening test for cobalamin deficiency and inherited methyl malonic acidemia. On the basis of the narrow range of normal concentration, it is expected that the method would readily detect mild cobalamin deficiency.

MeSH Terms

Chromatography, Gas*
Creatinine
Diagnosis
Gas Chromatography-Mass Spectrometry*
Humans
Infant, Newborn
Limit of Detection
Mass Screening
Metabolism
Methylmalonic Acid*
Methylmalonyl-CoA Mutase
Reference Values
Spectrum Analysis
Vitamin B 12
Vitamins
Creatinine
Methylmalonic Acid
Methylmalonyl-CoA Mutase
Vitamin B 12
Vitamins