NEURODEGENERATION AND DIABETES - UK NATIONWIDE STUDY OF WOLFRAM (DIDMOAD) SYNDROME
NEURODEGENERATION AND DIABETES - UK NATIONWIDE STUDY OF WOLFRAM (DIDMOAD) SYNDROME
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DOI：
10.1016/s0140-6736(95)92473-6
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发表时间：
1995-12-02
期刊：
影响因子：
168.9
通讯作者：
MACLEOD, AF
中科院分区：
文献类型：
--
作者：
BARRETT, TG;BUNDEY, SE;MACLEOD, AF
Wolfram综合征是糖尿病和视神经萎缩的关联，有时被称为DIDMOAD(尿崩症、糖尿病、视神经萎缩和耳聋)。这种常染色体隐性遗传综合征的不完全特征依赖于病例报告，并与线粒体基因组疾病混淆。因此，我们开展了一项英国全国范围的横断面病例查找研究，以描述该综合征的自然病史、并发症、患病率和遗传性。我们确定了45名Wolfram综合征患者--患病率为每770000人中就有一人。非自身免疫性、胰岛素缺乏性糖尿病的发病年龄中位数为6岁，其次是视神经萎缩(11岁)。33例(73%)感音神经性耳聋患者(28例，62%)在第二个十年出现颅脑尿崩症；第三个十年出现肾脏和肌束异常(26例，58%)；第四个十年出现神经系统并发症(小脑性共济失调、肌阵挛[28，62%])。其他异常包括11例(24%)胃肠动力障碍，以及10例男性中7例原发性腺萎缩。中位死亡年龄(通常为中枢性呼吸衰竭合并脑干萎缩)为30岁(25-49岁)。Wolfram综合征的自然病史表明，大多数患者最终将发展为这种进行性神经退行性疾病的大多数并发症。家系研究表明，常染色体隐性遗传的携带者频率为354%，没有母亲糖尿病或耳聋病史，也没有线粒体tRNA Leu(3243)突变。青少年起病的糖尿病和视神经萎缩是Wolfram综合征的最佳诊断标准，其鉴别诊断包括其他导致神经变性的原因。
Wolfram syndrome is the association of diabetes mellitus and optic atrophy, and is sometimes called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Incomplete characterisation of this autosomal recessive syndrome has relied on case-reports, and there is confusion with mitochondrial genome disorders. We therefore undertook a UK nationwide cross-sectional case-finding study to describe the natural history, complications, prevalence, and inheritance of the syndrome.We identified 45 patients with Wolfram syndrome-a prevalence of one per 770000. Non-autoimmune, insulin-deficient diabetes mellitus presented at a median age of 6 years, followed by optic atrophy (11 years). Cranial diabetes insipidus occurred in 33 patients (73%) with sensorineural deafness (28, 62%) in the second decade; renal;tract abnormalities (26, 58%) presented in the third decade followed by neurological complications (cerebellar ataxia, myoclonus [28, 62%]) in the fourth decade. Other abnormalities included gastrointestinal dysmotility in 11 (24%), and primary gonadal atrophy in seven of ten males investigated. Median age at death (commonly central respiratory failure with brain-stem atrophy) was 30 years (range 25-49).The natural history of Wolfram syndrome suggests that most patients will eventually develop most complications of this progressive, neurodegenerative disorder. Family studies indicate autosomal recessive inheritance with a carrier frequency of one in 354, an absence of a maternal history of diabetes or deafness, and an absence of the mitochondrial tRNA Leu (3243) mutation. Juvenile-onset diabetes mellitus and optic atrophy are the best available diagnostic criteria for Wolfram syndrome, the differential diagnosis of which includes other causes of neurodegeneration.