Urinary medium-chain acylcarnitines in medium-chain Acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: Sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography method

Abstract

To determine the sensitivity and specificity of detecting urinary medium-chain acylcarnitines for the diagnosis of MCAD deficiency, 114 urine specimens from 75 children with metabolic diseases and controls were analyzed in a blinded fashion using a radioisotopic ex-change/HPLC method. All 47 patients with MCAD deficiency were correctly diagnosed using the criterion hexan-oylcarnitine or octanoylcarnitine peak areas larger than those of other medium-chain acylcarnitines. The majority of them were tested during the asymptomatic state without L-carnitine loading. Four patients with other defects of fatty acid oxidation and three patients receiving valproic acid had a similar acylcarnitine excretion pattern. To further examine the specificity of the method, eight infants receiving a diet enriched with medium-chain triglycerides and 13 additional patients receiving valproic acid were j studied. Most of these also tested positive for MCAD, deficiency by the above criterion. Analysis by a new gas j chromatographic-mass spectrometric procedure revealed j that octanoylcarnitine, not valproylcarnitine, was the most] abundant medium-chain carnitine ester excreted by a pa-\tient treated with valproic acid. Quantitation of urinary i hexanoylcarnitine and octanoylcarnitine showed consider- < able overlap among patients with MCAD deficiency and 1 those receiving valproic acid or a medium-chain triglycer-ide-enriched diet. MCAD deficiency can be reliably de- i tected in urine specimens by this method without the need 1 for prior carnitine loading. However, other defects in fatty (acid oxidation must be differentiated from MCAD defi- 1 ciency, and a history of medium-chain triglyceride or val- < proic acid administration must be considered if the diag- ‘ nosis of MCAD deficiency is sought through analysis of] urinary acylcarnitines. © 1992 International Pediatric Research Foundation, Inc.