Abstract:

Objective　To investigate the clinical characteristics, gene mutation, and treatment of Fabry disease in two children from a family with neuropathic pain as the main clinical manifestation. Methods　The proband, an 11-year-old boy, was diagnosed with pain in both toes for more than 2 years in Jinan Children's Hospital in May 2021. His cousin, a 13-year-old boy, was diagnosed due to burning pain at the end of his toe for one year in Jinan Children's Hospital in July 2021. Peripheral blood samples were collected from the proband and his parents. LR-PCR and generation Ⅱ sequencing were used to determine the mutation gene locus in the pedigree. The clinical manifestation, diagnosis and treatment process of 2 cases were retrospectively analyzed after 1 year follow-up of enzyme replacement therapy. Results　The activity of α-galactosidase A (α-Gal A) was significantly decreased in both cases. The detection of GLA gene showed c.1080_1082delTGG hemizygous mutation, all of which originated from the mother. After one year of treatment, the clinical symptoms in both cases were relieved without recurrence, and the activity of α-Gal A in plasma returned to normal. Conclusion　We investigate the clinical characteristics, gene detection, and therapeutic principle of children with Fabry disease, to provide references for clinical diagnosis and treatment of Fabry disease in children.

Key words:

Fabry disease, α-galactosidase A, Gene mutation, Enzyme replacement therapy

摘要：

目的　对2例（表兄弟）以神经性疼痛为主要临床表现的法布雷病家系进行调查，探讨法布雷病的临床特点、基因突变及治疗情况。方法　先证者，男，11岁，因双脚趾疼痛2年余于2021年5月在济南市儿童医院就诊；其表哥，男，13岁，因脚趾末端烧灼样疼痛1年于2021年7月在济南市儿童医院就诊。抽取先证者及父母外周血，采用LR-PCR+Ⅱ代测序方法，确定家系突变基因位点。给予酶替代治疗，该2例患儿均给予阿加糖酶β 1.0 mg/kg，每2周静脉输注1次。随访1年回顾分析2例患儿的临床表现、诊疗过程。结果　2例患儿治疗3～4个月肢端疼痛缓解，半年复查三己糖酰基鞘脂醇的衍生物（Lyso-GL-3）均明显降低（先证者Lyso-GL-3结果为2.30 μg/L，其表哥Lyso-GL-3结果为1.30 μg/L），GLA基因检测发现c.1080_1082delTGG半合子突变，变异来源均为母亲。治疗1年2例患儿临床症状均缓解，无复发，血浆α-半乳糖苷酶Ａ（α-Gal A）活性恢复正常。结论　分析儿童法布雷病的临床特征、基因检测及治疗原则，以期为儿童法布雷病临床诊疗提供参考。

关键词:

 , 法布雷病, α-半乳糖苷酶Ａ, 基因突变, 酶替代治疗