早发型球形细胞脑白质营养不良的临床及基因分析1例报告

摘要

Objective To investigate the clinical, biochemical and genetic features of a Chinese boy with early-onset glo-boid cell leukodystrophy (GLD). Methods The clinical and genetic data of a rare case of early-onset GLD were retrospectively analysed. Results At 2 months after birth, the boy showed progressive psychomotor regression. At 4 months of age when the boy was taken to a doctor, the pyramidal sign was positive. The cranial MRI showed that the body of the lateral cerebral ventri-cles was slightly enlarged and the brain ditch crack of frontal-temporal-parietal lobe was widened and deepened. On his brain CT scan, high signals in bilateral basal ganglia, thalami, cerebellar hemisphere were observed.β-galactosylceramidase (GALC) ac-tivity in the peripheral leucocytes was signiifcantly decreased (3.9 nmol/g protein.h). On his GALC gene, one homozygous novel mutation c.868C>T on exon 8 was found, which resulted in the amino acid change on p.R290C proteins. Conclutions Early-on-set GLD is a rare autosomal-recessive hereditary lysosomal storage disease with a terrible prognosis, in which beta-galactose glu-coside enzyme deifciency is induced by GALC gene mutation. The diagnosis of early-onset GLD is dififcult and should depend on enzyme assay and gene testing.%目的：探讨球形细胞脑白质营养不良的临床及基因诊断。方法回顾性分析1例罕见的早发婴儿型球形细胞脑白质营养不良的临床及基因分析资料。结果患儿，男，于生后2个月进行性精神运动倒退；4个月就诊，锥体束征阳性；头颅MRI示双侧脑室体部略大，额颞顶叶脑沟裂宽深；头颅CT示双基底节区、丘脑、小脑半球稍高信号；外周血白细胞β-半乳糖苷酶活性降低为3.9 nmol/(g protein·h)；基因分析证实，GALC外显子8存在纯合的c.868C>T突变，为一新的错义突变，导致氨基酸改变p.R290C。结论早发型球形细胞脑白质营养不良是一种致死性常染色体隐性遗传性溶酶体贮积症，是由于GALC基因缺陷导致的β-半乳糖苷酶缺乏症；临床诊断困难，确诊需依靠酶学及基因分析。