当罕见病并非以单一疾病形式出现时

文献信息

中文摘要

目的：
年轻成人中出现多系统受累的共存情况，需要考虑罕见的代谢性和线粒体疾病。我们报告一例迟发性丙酸血症（PPA），该病可能促成了Leber遗传性视神经病变（LHON）的显现，这是一种极为罕见的关联。

病例介绍：
一名43岁女性在病毒感染后出现急性双心室心力衰竭。评估显示严重扩张型心肌病、新诊断的2型糖尿病和双侧感音神经性听力损失。心肌病基因检测无异常。两个月后，她因视神经病变出现突发双侧失明。扩展基因分析发现一个与LHON相符的致病性RDH12变异和两个POLG变异。进行性肾功能不全和长QTc间期促使进行代谢检查。尿有机酸显示丙酸相关代谢物显著蓄积，血浆酰基肉碱显示C3升高和游离肉碱降低，证实为迟发性PPA。心脏功能障碍、肾功能损害和听力损失的模式与PPA的慢性多系统毒性一致。

结论：
在该患者中，PPA引起的线粒体功能障碍可能促成了LHON的临床表达，而LHON是一种外显率不完全的疾病。这种罕见的共存提示罕见病可能重叠，且无法解释的多系统发现值得进行全面的代谢和遗传评估。

英文摘要

OBJECTIVES: The coexistence of multisystemic involvement in a young adult raises the need to consider rare metabolic and mitochondrial disorders. We report a case of late-onset propionic acidemia (PPA) that may have contributed to unmasking Leber hereditary optic neuropathy (LHON), an extremely infrequent association.
CASE PRESENTATION: A 43-year-old woman presented with acute biventricular heart failure following a viral infection. Evaluation revealed severe dilated cardiomyopathy, newly diagnosed type 2 diabetes mellitus, and bilateral sensorineural hearing loss. Genetic testing for cardiomyopathy was unremarkable. Two months later, she developed sudden bilateral blindness due to optic neuropathy. Extended genetic analysis identified a pathogenic RDH12 variant consistent with LHON and two POLG variants. Progressive renal dysfunction and long QTc interval prompted metabolic investigation. Urine organic acids showed marked accumulation of propionate-related metabolites, and plasma acylcarnitines revealed elevated C3 and low free carnitine, confirming late-onset PPA. The pattern of cardiac dysfunction, renal impairment, and hearing loss was consistent with chronic multisystem toxicity of PPA.
CONCLUSIONS: In this patient, mitochondrial dysfunction from PPA may have precipitated the clinical expression of LHON, a condition with incomplete penetrance. This exceptional coexistence highlights that rare diseases may overlap and that unexplained multisystem findings warrant comprehensive metabolic and genetic evaluation.