Clinical and genetic characteristics of adolescent and adult Krabbe disease
10.3760/cma.j.cn113694-20220829-00656
- VernacularTitle:青少年和成人型Krabbe病的临床与遗传学特点
- Author:
Ting XU
1
;
Zeyu ZHU
;
Jingying WU
;
Xiaojun HUANG
;
Li CAO
;
Wotu TIAN
Author Information
1. 上海交通大学附属第六人民医院神经内科，上海200233
- Keywords:
Leukodystrophy, globoid cell;
Gait apraxia;
Mutation;
GALC gene
- From:
Chinese Journal of Neurology
2022;55(11):1261-1269
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic characteristics of patients with late-onset subtypes (adolescent or adult) of Krabbe disease.Methods:The clinical data of 7 patients with Krabbe disease admitted to Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021 were analyzed and Sanger sequencing of the galactosylceramidase (GALC) gene (NM_000153) and detection of the activity of GALC were conducted. A total of 61 cases of Krabbe disease reported in domestic literature were reviewed and summarized.Results:Among the 7 patients with Krabbe disease, there were 4 males and 3 females. All of them had lower limb weakness or walking difficulty as the initial symptoms, and presented as spastic paraplegia. The symptoms were relatively mild in patients with late onset. There were 4 out of 5 patients undergoing magnetic resonance imaging examination, who showed abnormal signals: 2 had brain atrophy and the remaining 2 had white matter lesions. A total of 5 GALC gene mutations were detected by genetic analysis. Among these, c.1901T>C (p.L634S), c.908C>T(p.S303F) and c.461C>A(p.P154H) are known variants, while c.50_51insTT (p.M17Ifs) and c.1130delT(p.L337X) are novel variants reported for the first time in this paper.Conclusions:Krabbe disease is a rare neurodegenerative disease with phenotypic heterogeneity, which is inherited in an autosomal recessive mode. The severity of clinical manifestations of Krabbe disease is correlated with the age of onset.
