Cardiovascular involvement in later-onset malonyl-CoA decarboxylase deficiency: Case studies and literature review.

Emanuele Monda, Athanasios Bakalakos, Petros Syrris, Saidi Mohiddin, Sacha Ferdinandusse, Elaine Murphy, Perry Mark Elliott

Journal: European journal of medical genetics 2023;66(12):104885

PMID: 37979716

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Malonyl-CoA decarboxylase deficiency (MLYCDD) is an ultra-rare inherited metabolic disorder, characterized by multi-organ involvement manifesting during the first few months of life. Our aim was to describe the clinical, biochemical, and genetic characteristics of patients with later-onset MLYCDD.

METHODS

Clinical and biochemical characteristics of two patients aged 48 and 29 years with a confirmed molecular diagnosis of MLYCDD were examined. A systematic review of published studies describing the characteristics of cardiovascular involvement of patients with MLYCDD was performed.

RESULTS

Two patients diagnosed with MLYCDD during adulthood were identified. The first presented with hypertrophic cardiomyopathy and ventricular pre-excitation and the second with dilated cardiomyopathy (DCM) and mild-to-moderate left ventricular (LV) systolic dysfunction. No other clinical manifestation typical of MLYCDD was observed. Both patients showed slight increase in malonylcarnitine in their plasma acylcarnitine profile, and a reduction in malonyl-CoA decarboxylase activity. During follow-up, no deterioration of LV systolic function was observed. The systematic review identified 33 individuals with a genetic diagnosis of MLYCDD (median age 6 months [IQR 1-12], 22 males [67%]). Cardiovascular involvement was observed in 64% of cases, with DCM the most common phenotype. A modified diet combined with levocarnitine supplementation resulted in the improvement of LV systolic function in most cases. After a median follow-up of 8 months, 3 patients died (two heart failure-related and one arrhythmic death).

CONCLUSIONS

For the first time this study describes a later-onset phenotype of MLYCDD patients, characterized by single-organ involvement, mildly reduced enzyme activity, and a benign clinical course.

Address: Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; Institute of Cardiovascular Science, University College of London, London, UK. Electronic address: [email protected].; Institute of Cardiovascular Science, University College of London, London, UK.; Barts Health NHS Trust, London, UK; Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.; Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Charles Dent Metabolic Unit, The National Hospital for Neurology and Neurosurgery, London, UK.; Institute of Cardiovascular Science, University College of London, London, UK; Barts Health NHS Trust, London, UK.

DOI: 10.1016/j.ejmg.2023.104885

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MeSH Terms: Adult, Male, Cardiomyopathy, Hypertrophic, Cardiomyopathy, Dilated, Humans, Malonyl Coenzyme A, Metabolism, Inborn Errors, Carboxy-Lyases, Infant, Methylmalonic Acid