探讨Krabbe病临床特点、诊断及患儿预后。

选择2022年03月15日于甘肃省妇幼保健院就诊的1例Krabbe病患儿(患儿1)为研究对象。采用回顾性分析方法对其临床资料和影像学资料进行分析，并采用二代基因测序技术对患儿1及其父母进行基因检测；采用本研究设定的检索策略，对国内外数据库中Krabbe病相关研究进行文献复习。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》，监护人对患儿的诊治及基因检测均知情同意。

①患儿1，女性，4个月龄，主要临床表现为阵发性发热、易激惹、喂养困难、运动发育倒退及肌张力增高。视频脑电图监测可见其睡眠期左侧额、额极、中央中线、中后颞区较多低中波幅尖波、尖慢复合波阵发性同步簇发、散发。头颅MRI结果显示双侧小脑半球，双侧内囊后肢及双侧侧脑室旁可见对称性异常信号，呈长T1长T2信号。二代基因测序结果显示，患儿1的GALC基因有2个杂合突变，分别为c.908＋1(IVS8) G>A的剪接点突变(致病性突变)，以及c.194(exon1) G>A，导致氨基酸改变p.G65E，这2个突变分别来源于其母亲、父亲。患儿1被确诊为Krabbe病(早发婴儿型)。对患儿1未予特殊治疗，随访期内患儿1主要表现为喂养困难、异常姿势及反复呼吸道感染，于9个月龄时死亡。②文献复习结果：在国内外数据库中共计检索出7篇关于Krabbe病研究相关文献，涉及患儿11例(患儿2～12)，加上本研究患儿1，共计12例Krabbe病患儿。这12例患儿的主要临床表现为哭闹、喂养困难和精神运动发育倒退。

Krabbe病患儿主要临床表现为易激惹、喂养困难，精神运动发育迟缓或倒退。其头颅MRI表现为双侧对称性脑白质或内囊后肢异常信号，GALC基因突变有助于确诊该病患儿。对该病患儿迄今尚无特异性治疗措施，患儿预后差。

To investigate the clinical features, diagnosis and prognosis of Krabbe disease.

A child with Krabbe disease (patient 1) who was admitted to Gansu Provincial Maternity and Child-care Hospital on March 15, 2022 was selected as the research object. The clinical and imaging data were retrospectively analyzed, and the gene detection were performed on the patient 1 and her parents by next-generation sequencing technology. Using the retrieval strategy set in this study, the literature about Krabbe disease in domestic and foreign databases were reviewed. This study was in line with World Medical Association Declaration of Helsinki revised in 2013 and guardians informed and agreed to the diagnosis, treatment and genetic testing of the patient 1.

① Patient 1 was a 4-month-old girl who had the main clinical manifestations of paroxysmal fever, irritability, feeding difficulties, regression of motor development and increased muscle tone. Video electroencephalogram monitoring showed that there were many paroxysmal synchronous bursts and sporadic low-medium amplitude sharp waves and sharp-slow complex waves in the left frontal, frontal pole, central midline, middle and posterior temporal regions during sleep. Cranial MRI showed symmetrical abnormal signals in bilateral cerebellar hemispheres, bilateral posterior limb sets of internal capsule and bilateral lateral ventricles, showing long T1 and long T2 signals. The results of next-generation sequencing gene test showed that there were two heterozygous mutations in GALC gene of patient 1, namely, the splicing point mutation of c. 908+ 1(IVS8) G>A which was pathogenic mutation, and c. 194(exon1) G>A, which resulting in amino acid change of p. G65E. These two mutations were derived from her mother and father, respectively. Patient 1 was diagnosed with Krabbe disease (early-onset infantile type). No special treatments were given to patient 1. During the follow-up period, patient 1 mainly showed feeding difficulties, abnormal posture and recurrent respiratory tract infection, and died at 9 months of age. ② Results of literature review: a total of 7 pieces of literature related to Krabbe disease were retrieved from domestic and foreign databases, involving 11 children (patient 2-12), and patient 1 in this study, a total of 12 children with Krabbe disease. Their main manifestations were crying, feeding difficulties and regression of psychomotor development.

The main clinical manifestations of children with Krabbe disease are irritability, feeding difficulties, psychomotor retardation or regression. Cranial MRI showed bilateral symmetrical white matter or abnormal signal in the posterior limb of the internal capsule. GALC gene mutation is helpful for the diagnosis of the disease. There is no specific treatment for the disease, and the prognosis of the children with Krabbe disease is poor.