发作性瘫痪起病的亚历山大病1例报道并文献复习

Onset Alexander disease presenting with paroxysmal paralysis-a case report and review of the literatures

目的：分析总结少年型亚历山大病（Alexanderdisease，AD）这一罕见病的临床表现、影像学特点及基因突变，企以提高临床对本病的认识。方法：详细回顾1例少年AD患儿的临床资料，并结合相关文献进行讨论，总结少年AD的临床特征，包括发病年龄、肢体瘫痪、惊厥、球麻痹、共济失调、自主神经症状、头围增大及认知障碍等表现；分析神经影像学特点和胶原纤维酸性蛋白（GFAP）基因突变。结果：本例男性，年龄10岁零10个月，7岁零5个月时以左下肢瘫痪起病，病程呈发作性，缓慢加重，后发展为四肢痉挛性瘫痪，伴球麻痹、自主神经功能障碍。头颅磁共振检查（MRI）示额叶白质、脑室周围白质及延髓异常信号，脑室周围白质轻度强化。二代测序发现GFAP基因新生杂合突变：C．1073C〉T，P．A358V。本例为A358V错义突变，此位点之突变文献鲜见报道。结论：少年AD临床表现多样，缺乏特异性，MRl可表现为以额叶为主广泛大脑白质信号异常，伴基底节、脑干受累。对于儿童期起病，临床表现为瘫痪、球麻痹、共济失调、认知障碍及惊厥，伴上述头颅MRI特征患者，需高度警惕AD可能，必要时行基因检测明确诊断。

Objective：To analyze the clinical characteristics of the brain magnetic resonance.imaging （MRI） and genetic mutations of juvenile Alexander＇s disease （AD） in order to improve the cognition og such a rare disease for clinicians Methods：The clinical data of a patient with juvenile AD was analyzed, and a review about juvenile AD was summarized including the patient＇ s age of onset, paralysis, convul- sion, bulbar paralysis, ataxia, autonomic nerve symptoms, head circumference and cognitive impair- ment, etc. The MRI characteristics and collagen fiber characteristics of acidic protein （GFAP） gene mu- tations of the case were also analyzed. Results：The patient was a boy of 10 years and 10 months . His first complaint was the paralysis of the left leg when he was 7 years and 5 months old, and then the par- oxysmal exacerbation aceured including the monoplegia and limb spastic paralysis, bulbar palsy and dys- function of the autonomic nervous system. MRI showed white matter and medulla in the frontal lobe. The periventricular lesions showed the mild strengthen by the contrast scanning. The de novo heterozygous （c. 1073 C 〉 T） mutation in GFAP was identified. Meanwhile, in 66 reported juvenile AD cases（inclu- ding our patient） , the mean age at onset was 7.2 years old （2 years old -- 12. 4 years old）, The syn- dromes mainly contained limb paralysis（36.2%, 21/58）, convulsions（20. 6%, 12/58）, bulbar paralysis （56.9%, 33/58） , ataxia（29.3% ,17/58） , autonomic nerve symptoms（8.6% ,5/58） , macrocephalous（17.2%,10/58） and cognitive impairment（25.9%, 15/58）. But the symptoms of paroxysmal paralysis were not reported in the literature. 44 out of 66 （66.7%） cases received diagnosis of AD in the Brain MRI, and the characteristics were mainly bilateral in high signal-intensity areas in the frontal lobes and periventricular white matter, abnormal signals in the basal nuclei and brain stem （mainly the medulla ob- longata）, performed T1 weighted as low signals, high signals in the T2-weighted images and the contrast scanning, and the multiple lesions in medulla oblongata, cervical spinal atrophy or cerebellum abnomal. 33.3 % （22/66）cases did not receive the diagnosis of AD. The gene sequencing results of all the 66 cases revealed cases （98.2%） GFAP mutations in 57,in which 54 cases （94.7%） had missense mutation, hot spot mutations for R88C（13 cases ,22.8%） ,R239 （7 cases,12. 3%）, R79 （6 cases,10. 5%） , and R416W （5 cases, 8.8%）. A358V mutation occured in our patient, which was not reported until now. Conclusion ： The clinical features of juvenile AD is a complex disease,without definite characteristics. MRI mainly revealed abnormal images of white matter widely in the frontal lobe and basal nuclei and brain- stem. The AD should be considered when the patients manifest limb paralysls,bulbar paralysis, ataxia, cognitive impairment, convulsion and abnormity of the above brain MRI characteristics. The gene of GFAP should be detected for early diagnosis of AD.