Barrett T G, Bundey S E, Fielder A R, Good P A
Department of Clinical Genetics, Institute of Child Health, University of Birmingham, UK.
Eye (Lond). 1997;11 ( Pt 6):882-8. doi: 10.1038/eye.1997.226.
Wolfram syndrome is the association of diabetes mellitus and optic atrophy, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Incomplete characterisation has caused diagnostic confusion; we therefore undertook a nation-wide cross-sectional case finding study. We identified 45 patients with Wolfram syndrome, median age 29 years. All patients fulfilled the ascertainment criteria (juvenile onset diabetes mellitus and optic atrophy). Optic atrophy presented in 38 patients with reduced visual acuity and colour vision defect (median age 11 years), progressing to visual acuity of 6/60 or less in 35 patients (median time 8 years, range 1-25 years). Visual field examinations recorded before acuity deteriorated showed central scotomas with peripheral constriction. Blind patients had absent pupillary reflexes. Horizontal nystagmus was seen in patients with other signs of cerebellar degeneration. There was no pigmentary retinal dystrophy; only 3 patients had background diabetic retinopathy, despite a median duration of diabetes of 24 years. Electroretinography was normal in 3 patients and showed reduced amplitude in 3 patients; visual evoked responses were abnormal (10/10 patients: reduced amplitude to both flash and pattern stimulation). Magnetic resonance imaging showed generalised brain atrophy with reduced signal from the optic nerves and chiasm. A postmortem brain specimen from one patient revealed atrophy of the optic nerves, chiasm, cerebellum and brainstem. We found no evidence of mitochondrial genome defects or rearrangements. This primary neurogenerative disorder presents with diabetes mellitus and progressive optic atrophy, probably due to pathology in the optic nerve.
沃夫勒姆综合征是糖尿病与视神经萎缩的关联疾病，也称为 DIDMOAD（尿崩症、糖尿病、视神经萎缩和耳聋）。特征描述不完整导致了诊断上的混淆；因此，我们开展了一项全国性的横断面病例发现研究。我们确定了 45 例沃夫勒姆综合征患者，中位年龄为 29 岁。所有患者均符合确诊标准（青少年起病的糖尿病和视神经萎缩）。38 例患者出现视神经萎缩，伴有视力下降和色觉缺陷（中位年龄 11 岁），35 例患者的视力进展至 6/60 或更低（中位时间 8 年，范围 1 - 25 年）。在视力恶化之前进行的视野检查显示中央暗点伴周边收缩。失明患者瞳孔反射消失。在有其他小脑变性体征的患者中可见水平眼球震颤。没有视网膜色素变性；尽管糖尿病的中位病程为 24 年，但只有 3 例患者有糖尿病性视网膜病变背景。3 例患者的视网膜电图正常，3 例患者的视网膜电图显示波幅降低；视觉诱发电位异常（10/10 例患者：对闪光和图形刺激的波幅均降低）。磁共振成像显示全脑萎缩，视神经和视交叉信号减弱。一名患者的尸检脑标本显示视神经、视交叉、小脑和脑干萎缩。我们未发现线粒体基因组缺陷或重排的证据。这种原发性神经退行性疾病表现为糖尿病和进行性视神经萎缩，可能是由于视神经病变所致。
