Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, Permutt A, Halaby G
Departments of Endocrinology and Metabolism, Hôtel Dieu Hospital, Beirut, Lebanon.
J Clin Endocrinol Metab. 2004 Apr;89(4):1656-61. doi: 10.1210/jc.2002-030015.
Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). WFS seems to be a heterogeneous disease that has not yet been fully characterized in terms of clinical features and pathophysiological mechanisms because the number of patients in most series was small. In this study we describe 31 Lebanese WFS patients belonging to 17 families; this, to our knowledge, is the largest number of patients reported in one series so far. Criteria for diagnosis of WFS were the presence of insulin-dependent diabetes mellitus and optic atrophy unexplained by any other disease. Central diabetes insipidus was found in 87% of the patients, and sensorineural deafness confirmed by audiograms was present in 64.5%. Other less frequent features included neurological and psychiatric abnormalities, urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotropic hypogonadism in males, and diabetic microvascular disease. New features, not reported in previous descriptions, such as heart malformations and anterior pituitary dysfunction, were recognized in some of the patients and participated in the morbidity and mortality of the disease. Genetic analysis revealed WFS1 gene mutations in three families (23.5%), whereas no abnormalities were detected in mitochondrial DNA. In conclusion, WFS is a devastating disease for the patients and their families. More information about WFS will lead to a better understanding of this disease and hopefully to improvement in means of its prevention and treatment.
沃夫勒姆综合征（WFS）是一种罕见的遗传性神经退行性疾病，也被称为DIDMOAD（尿崩症、糖尿病、视神经萎缩和耳聋）。WFS似乎是一种异质性疾病，由于大多数病例系列中的患者数量较少，其临床特征和病理生理机制尚未得到充分描述。在本研究中，我们描述了来自17个家庭的31名黎巴嫩WFS患者；据我们所知，这是迄今为止在一个病例系列中报告的最大患者数量。WFS的诊断标准是存在胰岛素依赖型糖尿病和无法用任何其他疾病解释的视神经萎缩。87%的患者存在中枢性尿崩症，听力图证实的感音神经性耳聋在64.5%的患者中存在。其他不太常见的特征包括神经和精神异常、尿动力学异常、关节活动受限、心血管和胃肠道自主神经病变、男性高促性腺激素性性腺功能减退以及糖尿病微血管疾病。在一些患者中发现了先前描述中未报告的新特征，如心脏畸形和垂体前叶功能障碍，这些特征与疾病的发病率和死亡率有关。基因分析在三个家庭（23.5%）中发现了WFS1基因突变，而线粒体DNA未检测到异常。总之，WFS对患者及其家庭来说是一种毁灭性疾病。更多关于WFS的信息将有助于更好地理解这种疾病，并有望改善其预防和治疗方法。
