背景：乙基丙二酸脑病（EE）是一种罕见的中毒型代谢紊乱，多系统受累。它是由ETHE1中的突变引起的，ETHE1在线粒体基质中编码ETHE1酶，在硫化氢（H2S）解毒中起关键作用，充当硫双加氧酶。
结果：这篇综述侧重于临床，新陈代谢，70例报告病例的遗传和神经放射学特征，包括两个新病例。EE的常见表现是精神运动性回归，低张力,发育迟缓,瘀斑,锥体的迹象，慢性腹泻,立位性肢端发色和未能茁壮成长，分别。在经典表型和轻度表型之间，EMA和C4水平存在显着差异（p=0.003，p=0.0236）。尿EMA,发现C4和C5水平在无发作期的轻度病例中表现出正常值。最常见的ETHE1基因纯合状态突变是（p。R163Q）（c.488G>A），外显子4缺失,(p.R163W)(c.487C>T)，(p.Glu44ValfsTer62）（c.131_132delAG）和（p。M1I)(c.3G>T)突变，分别。52例患者接受了头颅MRI检查。42例检出基底节信号改变。在70个案例中，8例患者表型温和,神经系统进展缓慢,且乙基丙二酸(EMA)和C4酰基肉碱水平较低.在发表的具有轻度表型的文章中，活着的患者的当前年龄显着高于经典表型。（p=0.002）。减少硫化物的积累和诱导解毒是EE的主要长期治疗策略，包括甲硝唑,N-乙酰半胱氨酸(NAC),饮食调整，肝移植和连续肾脏替代治疗（CRRT）。
结论：在代谢发作期间测量EMA和C4酰基肉碱对诊断EE至关重要，允许早期开始治疗，以防止进一步的脑病危象。肝移植的经验，饮食和CRRT，目前有限。早期多学科联合治疗方法对于预防不可逆的神经损伤至关重要。
BACKGROUND: Ethylmalonic encephalopathy (EE) is a rare intoxication-type metabolic disorder with multisystem involvement. It is caused by mutations in ETHE1, which encodes the ETHE1 enzyme in the mitochondrial matrix that plays a key role in hydrogen sulfide (H2S) detoxification acting as a sulphur dioxygenase.
RESULTS: This
review focuses on the clinical, metabolic, genetic and neuroradiological features of 70 reported cases, including two new cases. The common manifestations of EE are psychomotor regression, hypotonia, developmental delay, petechia, pyramidal signs, chronic diarrhoea, orthostatic acrocyanosis and failure to thrive, respectively. A significant difference was found in EMA and C4 levels (p=0.003, p=0.0236) between classical and mild phenotypes. Urinary EMA, C4 and C5 levels were found to exhibit normal values in milder cases during attack-free periods. The most common ETHE1 gene homozygous state mutations were (p.R163Q) (c.488G>A), exon 4 deletion, (p.R163W)(c.487C>T), (p.Glu44ValfsTer62)(c.131_132delAG) and (p.M1I)(c.3G>T) mutations, respectively. Fifty-two patients underwent cranial MRI. Basal ganglia signal alterations were detected in 42 cases. Of the 70 cases, eight had a mild phenotype and slow neurological progression with low levels of ethylmalonic acid (EMA) and C4 acylcarnitine. The current age of alive patients in the published articles with mild phenotype was significantly higher than the classical phenotype. (p=0.002). Reducing the accumulation and inducing detoxification of sulfide is the main long-term treatment strategy for EE, including metronidazole, N-acetylcysteine (NAC), dietary modification, liver transplantation and continuous renal replacement therapy (CRRT).
CONCLUSIONS: Measuring EMA and C4 acylcarnitine during metabolic attacks is critical to diagnosing EE, allowing for early treatment initiation to prevent further encephalopathic crises. Experience with liver transplantation, diet and CRRT, is currently limited. An early multidisciplinary approach with combination therapies is vital to prevent irreversible neurological damage.
