BACKGROUND Propionic acidemia (PA) is an organic aciduria caused by inherited deficiency of propionyl-CoA carboxylase. Left ventricular dysfunction and QT prolongation may lead to life-threatening complications. Systematic analyses of cardiac phenotypes, in particular effects of specific cardiac therapies, are scarce. METHODS In this longitudinal observational monocentric study (data from 1989 to 2017) all PA patients treated at our center were included. Echocardiographic parameters (left ventricular end-diastolic diameter: LVEDD, left ventricular shortening fraction, mitral valve Doppler inflow pattern) and 12‑lead electrocardiogram recordings (corrected QT interval: QTc) were analyzed. Symptomatic patients were dichotomized to the group "early-onset" (symptoms within 28 days of life) and "late-onset" (symptoms after 28 days). Associations between cardiac function, LVEDD, QTc and clinical parameters (age at onset, beta-blocker or Angiotensin-converting enzyme inhibitor = ACE-I therapy) were analyzed. RESULTS 18 patients with PA were enrolled, 17 of them were symptomatic and one asymptomatic, with a median age at diagnosis of 6 days. 14/17 (82%) had early onset disease manifestation. Systolic left ventricular dysfunction (i.e. hypokinetic phenotype of cardiomyopathy) was diagnosed in 7/18 (39%) patients at a median age of 14.4 years, all had early onset. Two patients had a dilated left ventricle and systolic left ventricular dysfunction (i.e. dilated hypokinetic phenotype - dilated cardiomyopathy). Diastolic left ventricular dysfunction was found in 11/18 (61%) individuals, typically preceding systolic left ventricular dysfunction. ACE-I therapy did not improve systolic left ventricular function. Mean QTc was 445 ms (+/- 18.11 ms). Longer QTc was associated with larger LVEDD. CONCLUSIONS Systolic left ventricular dysfunction was found in 39% of patients, reflecting high disease severity. Two thirds of all individuals showed signs of diastolic left ventricular dysfunction usually preceding systolic left ventricular dysfunction; it therefore may be considered as an indicator for early cardiac disease manifestation, possibly allowing earlier treatment modification. Unresponsiveness to routine cardiac therapy highlights the need to evaluate further strategies, such as liver transplantation.

中文翻译：

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丙酸血症的心脏表型-一项观察性单中心研究的结果。

背景技术丙酸血症（PA）是由丙酰CoA羧化酶的遗传缺陷引起的一种有机酸尿症。左心功能不全和QT延长可能导致危及生命的并发症。缺乏对心脏表型的系统分析，特别是对特定心脏疗法的影响。方法在这项纵向观察性单中心研究（1989年至2017年的数据）中，纳入了我们中心治疗的所有PA患者。分析了超声心动图参数（左心室舒张末期直径：LVEDD，左心室缩短分数，二尖瓣多普勒流入模式）和12导联心电图记录（校正的QT间隔：QTc）。有症状的患者分为“早发”（生命28天内的症状）和“迟发”（28天后的症状）两类。分析了心脏功能，LVEDD，QTc与临床参数（发病年龄，β受体阻滞剂或血管紧张素转化酶抑制剂= ACE-1治疗）之间的关联。结果招募了18例PA患者，其中17例是有症状和1例无症状，中位年龄为6天。14/17（82％）具有早期发病的疾病表现。在中位年龄为14.4岁的7/18（39％）患者中诊断出收缩期左心室功能不全（即心肌病的低运动型）。两名患者的左心室扩张和收缩期左心室功能不全（即扩张的低运动型-扩张型心肌病）。在11/18（61％）的个体中发现舒张期左心室功能障碍，通常在收缩期左心室功能障碍之前。ACE-I治疗未改善收缩期左心室功能。平均QTc为445毫秒（+/- 18.11毫秒）。较长的QTc与较大的LVEDD相关。结论在39％的患者中发现收缩期左心室功能不全，反映出疾病的严重程度。所有个体中有三分之二表现出舒张期左心室功能障碍的迹象，通常在收缩期左心室功能障碍之前。因此，它可以被认为是早期心脏疾病表现的指标，可能允许更早进行治疗。对常规心脏疗法的无反应性凸显了需要评估其他策略（例如肝移植）的需求。反映疾病严重程度高。所有个体中有三分之二通常在收缩期左心室功能不全之前表现出舒张性左心室功能不全的征兆。因此，它可以被认为是早期心脏疾病表现的指标，可能允许更早进行治疗。对常规心脏疗法的无反应性凸显了需要评估其他策略（例如肝移植）的需求。反映疾病严重程度高。所有个体中有三分之二通常在收缩期左心室功能不全之前表现出舒张性左心室功能不全的征兆。因此，它可以被认为是早期心脏疾病表现的指标，可能允许更早进行治疗。对常规心脏疗法的无反应性凸显了需要评估其他策略（例如肝移植）的需求。