目的 探讨婴儿型Sandhoff病的临床表现、诊断及治疗.方法 回顾分析1例婴儿型Sandhoff病患儿的临床资料,并复习相关文献.结果 1岁2个月女性患儿,有神经运动发育倒退、顽固性抽搐;父母为近亲婚配;眼底镜检查见眼底红斑;头颅磁共振成像示左侧脑桥可见一小点状长T 2等T 1异常信号影,脑白质水肿、弥漫性脱髓鞘改变;染色体核型未见异常;染色体微阵列提示多条染色体发生大片段纯合子;二代基因测序提示HEXB基因外显子11存在c.1263_1268delTGAAGT:P.(Glu422_Val423del)缺失突变及内含子13存在c.1614_2A>G:P?剪切突变,父母各携其一.白细胞HexA、HexA&HexB酶活性分别为84、112 nmol/(mg·h);确诊为婴儿型Sandhoff病.治疗采用丙戊酸钠、左乙拉西坦联合抗癫痫及糖皮质激素,患儿抽搐发作次数逐渐减少,反应较前好转;随访5个月,病情平稳无进展,无抽搐发作.患儿母亲再次妊娠,并于孕21+6周时行羊水穿刺检查,结果提示胎儿与患儿存在相同的突变.结论 Sandhoff病是一种罕见的遗传性溶酶体病,主要表现为进行性神经功能损害,目前缺乏有效的治疗方法,基因检测有助确诊及产前诊断.%Objective To summarize the clinical manifestations, diagnosis, and treatment of infantile Sandhoff disease. Methods The clinical data of one case with infantile Sandhoff disease were reviewed retrospectively. The related literatures were reviewed. Results The girl aged 1 year and 2 months suffered from psychomotor regression and intractable convulsions. The parents were consanguineous marriage. The fundus microscopy showed fundus erythema. Brain magnetic resonance imaging showed an abnormal signal of long T2WI and identical T1WI at left pons, white matter edema, and diffuse demyelination. No abnormal karyotype was observed. A chromosome microarray suggested multiple large homozygous chromosomes segments. The second generation gene sequencing showed deletion of c.1263_1268delTGAAGT:P. (Glu422_Val423del) deletion in exon 11 and a shear mutation of c.1614_2A>G:P? in intron 13 of HEXB gene which were carried by her parents respectively . The activity of HexA, HexA & HexB were 84 and 112 nmol?mg?1?h?1, respectively. Finally, this girl was diagnosed of infantile Sandhoff's disease. After treatment with valproate, levetiracetam combined with antiepileptic and glucocorticoids, episodes of convulsions were decreased gradually, and the reaction was better than before. In 5 months of follow up, the condition was stable, and no progression and no seizures exist. Her mother got pregnant again and received an amniocentesis on her 21+6 weeks of pregnancy, and results suggest that the fetus had the same mutation as this girl. Conclusions Sandhoff's disease is a type of rare hereditary lysosomal disease, characterized by progressive neurological impairment. Currently there are no effective treatments. Genetic testing is helpful in the diagnosis and prenatal diagnosis.
展开▼
