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.
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.
摘要：
背景：丙二酰辅酶A脱羧酶缺乏症（MLYCDD）是一种非常罕见的遗传性代谢紊乱，在生命的最初几个月表现为多器官受累。我们的目的是描述临床，生物化学，晚发性丙二酰辅酶A脱羧酶缺乏症患者的遗传特征。
方法：检查了两名年龄分别为48岁和29岁的患者的临床和生化特征，这些患者被确诊为MLYCDD。对已发表的描述MLYCDD患者心血管受累特征的研究进行了系统评价。
结果：确定了两名在成年期诊断为MLYCDD的患者。第一种表现为肥厚型心肌病和心室预激，第二种表现为扩张型心肌病（DCM）和轻度至中度左心室（LV）收缩功能障碍。未观察到其他典型的MLYCDD临床表现。两名患者均显示血浆酰基肉碱中丙二酰肉碱略有增加，和丙二酰辅酶A脱羧酶活性的降低。随访期间,未观察到LV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[IQR1-12]，22名男性[67%])。在64％的病例中观察到心血管受累，DCM是最常见的表型。在大多数情况下，改良饮食与左卡尼汀补充剂相结合可改善LV收缩功能。中位随访8个月后，3例患者死亡（2例心力衰竭相关死亡和1例心律失常死亡）。
结论：这项研究首次描述了MLYCDD患者的后期发病表型，以单器官受累为特征，酶活性轻度降低，和良性的临床过程。
方法：检查了两名年龄分别为48岁和29岁的患者的临床和生化特征，这些患者被确诊为MLYCDD。对已发表的描述MLYCDD患者心血管受累特征的研究进行了系统评价。
结果：确定了两名在成年期诊断为MLYCDD的患者。第一种表现为肥厚型心肌病和心室预激，第二种表现为扩张型心肌病（DCM）和轻度至中度左心室（LV）收缩功能障碍。未观察到其他典型的MLYCDD临床表现。两名患者均显示血浆酰基肉碱中丙二酰肉碱略有增加，和丙二酰辅酶A脱羧酶活性的降低。随访期间,未观察到LV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[IQR1-12]，22名男性[67%])。在64％的病例中观察到心血管受累，DCM是最常见的表型。在大多数情况下，改良饮食与左卡尼汀补充剂相结合可改善LV收缩功能。中位随访8个月后，3例患者死亡（2例心力衰竭相关死亡和1例心律失常死亡）。
结论：这项研究首次描述了MLYCDD患者的后期发病表型，以单器官受累为特征，酶活性轻度降低，和良性的临床过程。
