Plasma carnitine concentrations in Medium‐chain acyl‐CoA dehydrogenase deficiency: lessons from an observational cohort study

Our aim was to study the effect of secondary carnitine deficiency (SCD) and carnitine supplementation on important outcome measures for persons with medium‐chain Acyl–CoA dehydrogenase deficiency (MCADD). We performed a large retrospective observational study using all recorded visits of persons with MCADD in the University Medical Center Groningen, the Netherlands, between October 1994 and October 2019. Frequency and duration of acute unscheduled preventive hospital visits, exercise tolerance, fatigue, and muscle pain were considered important clinical outcomes and were studied in relation to (acyl)carnitine profile and carnitine supplementation status. The study encompassed 1228 visits of 93 persons with MCADD. >60% had SCD during follow‐up. This included only persons with severe MCADD. Carnitine supplementation and SCD were unrelated to the frequency and duration of the acute unscheduled preventive hospital visits (P > 0.05). The relative risk for fatigue, muscle ache, or exercise intolerance was equal between persons with and without SCD (RR 1.6, 95% CI 0.48–5.10, P = 0.4662). No episodes of metabolic crisis were recorded in non‐carnitine‐supplemented persons with MCADD and SCD. In some persons with MCADD, SCD resolved without carnitine supplementation. There is absence of real‐world evidence in favor of routine carnitine analysis and carnitine supplementation in the follow‐up of persons with MCADD.