TY - JOUR
T1 - Cardiovascular involvement in later-onset malonyl-CoA decarboxylase deficiency
T2 - Case studies and literature review
AU - Monda, Emanuele
AU - Bakalakos, Athanasios
AU - Syrris, Petros
AU - Mohiddin, Saidi
AU - Ferdinandusse, Sacha
AU - Murphy, Elaine
AU - Elliott, Perry Mark
N1 - Funding Information: None. Publisher Copyright: © 2023 Elsevier Masson SAS
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Dilated cardiomyopathy
KW - Hypertrophic cardiomyopathy
KW - Malonyl-CoA decarboxylase deficiency
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85177870051&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ejmg.2023.104885
DO - https://doi.org/10.1016/j.ejmg.2023.104885
M3 - Article
C2 - 37979716
SN - 1769-7212
VL - 66
JO - European journal of medical genetics
JF - European journal of medical genetics
IS - 12
M1 - 104885
ER -