MEDIUM-CHAIN ACYL-COA DEHYDROGENASE (MCAD) DEFICIENCY - DIAGNOSIS BY ACYLCARNITINE ANALYSIS IN BLOOD

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is a diso rder of fatty acid catabolism, with autosomal recessive inheritance. T he disease is characterized by episodic illness associated with potent ially fatal hypoglycemia and has a relatively high frequency. A rapid and reliable method for the diagnosis of MCAD deficiency is highly des irable. Analysis of specific acylcarnitines was performed by isotope-d ilution tandem mass spectrometry on plasma or whole blood samples from 62 patients with MCAD deficiency. Acylcarnitines were also analyzed i n 42 unaffected relatives of patients with MCAD deficiency and in othe r groups of patients having elevated plasma C8 acylcarnitine, consisti ng of 32 receiving valproic acid, 9 receiving medium-chain triglycerid e supplement, 4 having multiple acyl-coenzyme A dehydrogenase deficien cy, and 8 others with various etiologies. Criteria for the unequivocal diagnosis of MCAD deficiency by acylcarnitine analysis are an elevate d C8-acylcarnitine concentration (>0.3 muM), a ratio of C8/C10 acylcar nitines of >5, and lack of elevated species of chain length >C10. Thes e criteria were not influenced by clinical state, carnitine treatment, or underlying genetic mutation, and no false-positive or false-negati ve results were obtained. The same criteria were also successfully app lied to profiles from neonatal blood spots retrieved from the original Guthrie cards of eight patients. Diagnosis of MCAD deficiency can the refore be made reliably through the analysis of acylcarnitines in bloo d, including presymptomatic neonatal recognition. Tandem mass spectrom etry is a convenient method for fast and accurate determination of all relevant acylcarnitine species.