Engelmann G, Meyburg J, Shahbek N, Al-Ali M, Hairetis M H, Baker A J, Rodenburg R J T, Wenning D, Flechtenmacher C, Ellard S, Smeitink J A, Hoffmann G F, Buchanan C R
Department of General Paediatrics, University of Heidelberg, Im Neuenheimer Feld 153, Heidelberg, 69120, Baden-Württemberg, Germany.
J Inherit Metab Dis. 2008 Aug;31(4):540-6. doi: 10.1007/s10545-008-0867-0. Epub 2008 Aug 16.
A 10-year-old Arabic boy of consanguineous parents has suffered eight episodes of acute liver failure with haemolysis triggered by intercurrent febrile illnesses. The first crisis occurred at 9 months of age, after which diabetes mellitus developed. By the age of 6 years, short stature, mild myopathy and later skeletal epiphyseal dysplasia also became evident. His psychosocial development and educational achievements have remained within normal limits. While there were no clear biochemical indicators of a mitochondrial disorder, an almost complete deficiency of complex I of the respiratory chain was demonstrated in liver but not in fibroblast or muscle samples. Molecular analysis of the eukaryotic translation initiation factor 2alpha kinase gene (EIF2AK3) demonstrated a homozygous mutation, compatible with a diagnosis of Wolcott-Rallison syndrome (WRS). This patient's course adds a new perspective to the presentation of WRS caused by mutations in the EIF2AK3 gene linking it to mitochondrial disorders: recoverable and recurrent acute liver failure. The findings also illustrate the diagnostic difficulty of mitochondrial disease as it cannot be excluded by muscle or skin biopsy in patients presenting with liver disease. The case also further complicates the decision-making process for liver transplantation in cases of acute liver failure in the context of a possible mitochondrial disorder. Such patients may be more likely to recover spontaneously if a mitochondrial disorder underlies the liver failure, yet without neurological features liver transplantation remains an option.
一名10岁的阿拉伯男孩，其父母为近亲结婚，因并发发热性疾病引发了8次急性肝衰竭并伴有溶血。首次危机发生在9个月大时，之后患上了糖尿病。到6岁时，身材矮小、轻度肌病以及后来的骨骼骨骺发育异常也变得明显。他的心理社会发展和学业成绩仍在正常范围内。虽然没有线粒体疾病的明确生化指标，但在肝脏中发现呼吸链复合体I几乎完全缺乏，而在成纤维细胞或肌肉样本中未发现。对真核翻译起始因子2α激酶基因（EIF2AK3）的分子分析显示存在纯合突变，符合沃科特 - 拉利森综合征（WRS）的诊断。该患者的病程为EIF2AK3基因突变导致的WRS表现增添了新视角，将其与线粒体疾病联系起来：可恢复和复发性急性肝衰竭。这些发现还说明了线粒体疾病的诊断困难，因为在患有肝病的患者中，肌肉或皮肤活检无法排除该病。该病例也使在可能存在线粒体疾病的情况下急性肝衰竭患者的肝移植决策过程更加复杂。如果肝衰竭是由线粒体疾病引起的，这类患者可能更有可能自发恢复，但如果没有神经学特征，肝移植仍是一种选择。
