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

doi:10.1016/j.ejmg.2023.104885

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

Eur J Med Genet. 2023 Dec;66(12):104885. doi: 10.1016/j.ejmg.2023.104885. Epub 2023 Nov 17.

Authors

Emanuele Monda¹, Athanasios Bakalakos², Petros Syrris², Saidi Mohiddin³, Sacha Ferdinandusse⁴, Elaine Murphy⁵, Perry Mark Elliott⁶

Affiliations

¹ 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: emanuelemonda@me.com.
² Institute of Cardiovascular Science, University College of London, London, UK.
³ Barts Health NHS Trust, London, UK; Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁴ Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
⁵ Charles Dent Metabolic Unit, The National Hospital for Neurology and Neurosurgery, London, UK.
⁶ Institute of Cardiovascular Science, University College of London, London, UK; Barts Health NHS Trust, London, UK.

PMID: 37979716
DOI: 10.1016/j.ejmg.2023.104885

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.

Keywords: Dilated cardiomyopathy; Hypertrophic cardiomyopathy; Malonyl-CoA decarboxylase deficiency; Prognosis.

Publication types

Systematic Review

MeSH terms

Adult
Cardiomyopathy, Dilated*
Cardiomyopathy, Hypertrophic*
Humans
Infant
Male
Metabolism, Inborn Errors* / genetics
Methylmalonic Acid

Substances

Methylmalonic Acid
acylcarnitine

Supplementary concepts

Malonic aciduria