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

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY
Emanuele Monda , Athanasios Bakalakos , Petros Syrris , Saidi Mohiddin , Sacha Ferdinandusse , Elaine Murphy , Perry Mark Elliott
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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.

迟发性丙二酰辅酶a脱羧酶缺乏症对心血管的影响:病例研究和文献综述。
背景:丙二酰辅酶a脱羧酶缺乏症(Malonyl-CoA decarboxylase deficiency, mlcdd)是一种极其罕见的遗传性代谢疾病,其特征是在生命的最初几个月表现为多器官受累。我们的目的是描述晚发型丙二酰辅酶a脱羧酶缺乏症患者的临床、生化和遗传特征。方法:对2例年龄分别为48岁和29岁的分子诊断为MLYCDD的患者的临床和生化特征进行分析。对已发表的研究进行了系统回顾,描述了MLYCDD患者心血管受累的特征。结果:2例患者在成年期被诊断为MLYCDD。前者表现为肥厚性心肌病和心室预兴奋,后者表现为扩张性心肌病(DCM)和轻至中度左心室收缩功能障碍。未观察到其他典型的MLYCDD临床表现。两例患者血浆酰基肉碱谱均显示丙二酰肉碱轻微升高,丙二酰辅酶a脱羧酶活性降低。随访期间未见左室收缩功能恶化。系统评价确定了33例遗传诊断为MLYCDD的个体(中位年龄6个月[IQR 1-12], 22例男性[67%])。在64%的病例中观察到心血管受累,其中DCM是最常见的表型。在大多数情况下,改良饮食和补充左卡尼汀可改善左室收缩功能。中位随访8个月后,3例患者死亡(2例与心力衰竭相关,1例心律失常死亡)。结论:本研究首次描述了MLYCDD患者的晚发表型,其特征是单器官受累,酶活性轻度降低,临床病程为良性。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
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