摘要
Fabry病是由于溶酶体水解酶α-半乳糖苷酶A基因缺陷导致的X连锁隐性脂质贮积病,患者体内酰基鞘鞍醇三己糖进行性贮积,导致周围神经性疼痛,心、脑、肾、眼等多脏器损害,严重者可于青壮年死亡。但由于临床表现缺乏特异性,Fabry病早期诊断困难。本文报道1例男性患儿,4岁起出现双脚脚趾间断性刀割样疼痛,近2年加重伴双手手指胀痛,11岁时来院就医。患儿病程7年,曾接受多种止痛药物治疗无效,尚未出现心、脑、肾、皮肤、眼等脏器合并症,常规生化、免疫、肌电图、神经传导速度、脑影像学检查未见异常,诊断困难。外周血白细胞α-半乳糖苷酶A活性显著降低[1.0 nmol/(h.mg protein),正常对照值24.5～86.1 nmol(h.mg protein)],符合Fabry病诊断。基因分析显示,患儿α-半乳糖苷酶A基因IVS6+2 T>C剪切突变,其母亲及妹妹未携带相同突变,证实IVS6+2 T>C为新发突变。我国Fabry病发生情况不详,患者多起病隐匿,随着疾病进展逐渐出现发作性肢体疼痛及多脏器严重损害,引起尿毒症、心肌病、卒中,残障率及死亡率很高,早期的鉴别诊断至关重要。α-半乳糖苷酶活性检测是诊断Fabry病的关键,基因突变分析有助于确诊并指导家系的遗传咨询。
Fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of ct-galactosidase A （GLA）. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascu-lar dysfunction. Patients of severe cases die young. It has been proved that enzyme replacement therapy is a useful method to treat patients with Fabry disease. But the clinical diagnosis of the patients may often be difficult because of the lack of specific symptoms. In this study, a Chinese boy was diagnosed as Fabry disease at the age of 11 years with episodic pain for 7 years. The boy described the onset, at the age of 4 years, of episodic burning pain in the toes. Generalized aching and pain in the feet became progressive in the past two years and his hands were also affected. Divers analgesics were tried without effects. When he was admitted at the age of 11 years, none of complications was found in his heart, brain, kidneys, skin and eyes by routine laboratory examinations. Significantly decreased GLA activity of peripheral leucocytes [ 1.0 nmol/（ h · mg protein） vs. normal control 24.5 to 86.1 nmol/（ h · mg protein） ] supported the di-agnosis of Fabry disease. A splicing mutation IVS6 ＋ 2 T 〉 C was identified on his GLA gene. But it was not found in his mother and younger sister. The incidence of Fabry disease is not clear in Mainland Chi-na. The patients usually have insidious onset with complex and non-specific clinical manifestations. Stroke, uremia, cardiomyopathy and multiple organ dysfunctions are common at the late stage. Early di-agnosis is the key point to reduce the mortality and handicap. GLA enzyme activity is important to the di-agnosis of Fabry disease. The mutation analysis of GLA gene is helpful for genetic counseling.
出处
《北京大学学报（医学版）》
CAS
CSCD
北大核心
2013年第2期307-311,共5页
Journal of Peking University:Health Sciences
基金
"十二五"国家科技支撑计划重点项目(2012BAI09B04)资助~~
关键词
溶酶体贮积病
法布里病
α半乳糖苷酶
神经痛
酶替代治疗
Lysosomal storage diseases
Fabry disease
Alpha-galactosidase
Neuralgia
Enzyme re-placement therapy
