Medium-chain acyl-CoA dehydrogenase (
MCAD) deficiency, one of the most common inherited metabolic disorders, is often mistaken for the
sudden infant death syndrome or
Reye's syndrome. Diagnosing it has been difficult because of a lack of fast and reliable diagnostic methods. We developed a stable-
isotope dilution method to measure urinary n-
hexanoylglycine,
3-phenylpropionylglycine, and
suberylglycine, and we retrospectively tested its accuracy in diagnosing
MCAD deficiency. We measured the concentrations of these three acylglycines in 54 urine samples from 21 patients with confirmed
MCAD deficiency during the acute and asymptomatic phases of the illness and compared the results with the concentrations in 98 samples from healthy controls and patient controls with various diseases. The levels of urinary
hexanoylglycine and phenylpropionylglycine were significantly increased in all samples from the patients with
MCAD deficiency, clearly distinguishing them from both groups of controls. Although urinary
suberylglycine was increased in the patients, the range of values in the normal controls who were receiving formula containing medium-chain
triglycerides was very wide, overlapping somewhat with the values in the patients with asymptomatic
MCAD deficiency. These results indicate that the measurement of urinary
hexanoylglycine and phenylpropionylglycine by our method is highly specific for the diagnosis of
MCAD deficiency. The method is fast and can be applied to random urine specimens, without any pretreatment of patients.