GALC基因变异致早发婴儿型Krabbe病1例并文献复习  

Early-onset infantile Krabbe disease caused by GALC gene mutation:case report and literature review

作　　者：阴晓伟 刘芳 吕少广 杨梦迪 Yin Xiaowei;Liu Fang;Lyu Shaoguang;Yang Mengdi(Department of Neonatology,980th Hospital of PLA Joint Logistic Support Force,Shijiazhuang 050082,China)

机构地区：[1]解放军联勤保障部队第980医院新生儿科,石家庄050082

出　　处：《中华新生儿科杂志（中英文）》2024年第8期475-479,共5页Chinese Journal of Neonatology

基　　金：石家庄市科学技术研究与发展计划项目(201460703)。

摘　　要：目的总结Krabbe病的临床特征和基因型,加强临床医生对该病的认识。方法对解放军联勤保障部队第980医院新生儿科收治的1例早发婴儿型Krabbe病患儿的临床资料进行回顾性分析。以“Krabbe病”“GALC基因”“Krabbe disease”“infant”为关键词,分别对中国知网、维普数据库、万方数据库、中华医学期刊全文数据库、PubMed、Embase、Web of Science、Cochrane Library自建库以来至2023年8月31日收录的文献进行检索,总结早发婴儿型Krabbe病的临床特征和致病基因。结果本例患儿为胎龄36周男婴,生后48 d出现异常哭闹,哭闹时身体强直、肌张力增高,入院日龄54 d,体重5000 g(P 90),头围34 cm(<P 3),无追视,头颅CT提示严重脑萎缩,头颅MRI提示双侧基底节区对称性软化灶,血半乳糖脑苷脂酶活力明显降低,全外显子基因检测结果显示患儿GALC基因存在复合杂合变异,c.1901(exon16)T>C、upstream-62(inter-genetic)_upstream-57(inter-genetic)delATCAGC,来源于父亲,c.1685(exon15)T>C来源于母亲。患儿入院后出现抽搐,予左乙拉西坦、托吡酯抗癫痫治疗,同时给予康复治疗,随访至7月龄,智力、运动发育明显落后,仍有间断癫痫发作,多次患吸入性肺炎。共检索到7篇文献,包括本例共60例患儿,均存在神经系统症状,肌张力增高或强直23例(38.3%),异常哭闹、易激惹13例(21.7%),神经系统发育倒退13例(21.7%),抽搐5例(8.3%),喂养困难、易呛咳4例(6.7%),小头畸形3例(5.0%),眼球震颤、无追视追听2例(3.3%),耳聋、视觉丧失1例(1.7%),高血压、多汗1例(1.7%)。提及预后的22例患儿中2岁前死亡19例,2岁后死亡2例,1例为本患儿。60例患儿共发现GALC基因变异位点64个,其中纯合变异位点4个,杂合变异位点60个,以c.1161+6532_polyA+9kbdel V杂合变异报道最多。结论早发婴儿型Krabbe病于生后6个月内起病,以肌张力增高、异常哭闹、易激惹、神经系统发育倒退、喂养困难等�ObjectiveTo study the clinical characteristics and genotypes of Krabbe disease for better understanding of the disease.MethodsThe clinical data of a patient with early-onset infantile Krabbe disease admitted to the Department of Neonatology of our hospital were retrospectively analyzed.Using keywords"Krabbe disease""GALC gene"and"infant"(both in Chinese and English),multiple medical databases were searched from the inception to August 31,2023.Clinical features and genetic profiles of early-onset infantile Krabbe disease were summarized.ResultsOur patient was a boy with gestational age 36 weeks.Abnormal crying occurred 48 d after birth with body rigidity and increased muscle tone during crying.The age of admission was 54 d with body weight 5000 g(P 90)and head circumference 34 cm(<P 3).The patient had no pursuit gaze.Brain CT indicated severe brain atrophy and MRI showed bilateral symmetric malacia foci in basal ganglia.Blood galactocerebrosidase(GALC)decreased significantly.Whole exon sequencing(WES)showed compound heterozygous variations in GALC gene,c.1901(exon 16)T>C,upstream-62(inter-genetic)_upstream-57(inter-genetic)delATCAGC,from the father and c.1685(exon 15)T>C from the mother.After admission,the patient developed convulsions and levetiracetam,topiramate with rehabilitation treatment were initiated.The patient was followed up to 7 months old with significantly delayed intellectual and motor development.He still had intermittent seizures and suffered from aspiration pneumonia several times.A total of 7 literatures were retrieved with 60 cases(our case included).All cases had neurological symptoms,including 23(38.3%)increased muscle tone or rigidity,13(21.6%)abnormal crying and irritability,13(21.6%)nervous system development regression,5(8.3%)convulsions,4(6.7%)feeding difficulties and easily coughing,3(5.0%)microcephaly,2(3.3%)nystagmus,1(1.7%)deafness and visual loss and 1(1.7%)hypertension and hyperhidrosis.Among the 22 patients with recorded prognosis,19 died before 2 years old,2 died after 2 years ol

关 键 词：Krabbe病 GALC基因 哭闹 小头畸形 

分 类 号：R722.1[医药卫生—儿科]