NAXE基因突变相关渐进性早发性脑病的临床及遗传学特点

Clinical and genetic features of early-onset progressive encephalopathy associated with NAXE gene mutations

渐进性早发性脑病是由于NAXE基因变异导致的致死性脑病。本研究报道1例渐进性早发性脑病的临床和遗传性特征。患儿,男,4岁,因行走不稳,肢体无力2年就诊。患儿及其兄(已去世)均在2岁左右起病,均表现为斜视、共济失调、肌张力降低、发育落后,且感染后多次出现呼吸衰竭。患儿NAXE基因存在新发复合杂合突变:c.255(外显子2)A>T来自患儿母亲,c.361(外显子3)G>A来自患儿父亲。NAXE基因编码NADHX和NADPHX细胞代谢产物修复所必需的差向异构酶。本病存在线粒体NAD(P)HX修复系统的缺陷,进展快,极易在感染后迅速出现呼吸衰竭。

Early-onset progressive encephalopathy is a lethal encephalopathy caused by NAXE gene mutations. This paper reports the clinical and genetic features of a patient with early-onset progressive encephalopathy. A 4-yearold boy admitted to the hospital had repeated walking instability and limb weakness for 2 years. The patient and his elder brother（already dead） had clinical onset at 2 years of age. Both of them showed symptoms such as strabismus, ataxia, reduced muscle tone, delayed development, and repeated respiratory failure after infection. The NAXE gene of the patient showed new compound heterozygous mutations, i.e., c.255（exon 2） AT from his mother and c.361（exon 3） GA from his father. The NAXE gene encodes an epimerase that is essential for the repair of cellular metabolites of NADHX and NADPHX. This disease is associated with a deficiency of the mitochondrial NAD（P）HX repair system. Patients usually have rapid disease progression. They are also quite likely to have respiratory failure immediately after infection.