Tachycardiomyopathy-like presentation in neonatal MCAD deficiency: A novel cardiac phenotype

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder in Europe. Clinical onset typically occurs between 3 and 24 months of life with hypoketotic hypoglycemia, while neonatal presentations are less common. Although the disorder classically manifests with metabolic decompensation, atypical cardiac involvement has occasionally been reported but remains exceedingly rare. MCADD is included in many newborn screening programs, enabling early detection and timely management.

We report a full-term female neonate who, at 3 days of life, developed severe metabolic decompensation with refractory supraventricular tachyarrhythmias, severe systolic dysfunction, and biventricular dilation requiring maximal inotropic support. Expanded newborn screening revealed a profile consistent with MCADD, and genetic testing identified a homozygous variant in the ACADM gene, described according to HGVS nomenclature as ACADM(NM_000016.6):c.985A > C p.(Lys329Gln). Disease-specific management, including high-rate intravenous glucose administration, carnitine supplementation, and a tailored low-fat diet, resulted in complete normalization of cardiac function within 48 hours.

This case represents a tachycardiomyopathy-like presentation of neonatal-onset MCADD, a novel and rarely described cardiac phenotype. It emphasizes the importance of considering fatty acid oxidation disorders in the differential diagnosis of unexplained arrhythmias and cardiomyopathy in neonates, particularly before newborn screening results are available.

Early diagnosis and prompt initiation of metabolic treatment are essential to reverse potentially life-threatening cardiac manifestations in MCADD. This report highlights a novel phenotype and expands the clinical spectrum of neonatal-onset MCADD.