Diabetes Center, Children's Hospital AUF DER BULT, Hannover, Germany.
Centre of Reproductive Medicine and Andrology, Department of Clinical and Surgical Andrology, University of Münster, Muenster, Germany.
Endocrine. 2021 Mar;71(3):626-633. doi: 10.1007/s12020-021-02622-3. Epub 2021 Feb 1.
Wolfram Syndrome is a very rare genetic disease causing diabetes mellitus, blindness, deafness, diabetes insipidus, and progressive brainstem degeneration. Neurologic symptoms of affected patients include ataxia, sleep apnea, loss of bladder control, dysphagia, loss of taste, and accompanying psychiatric symptoms as a sign of progressive neurodegeneration. Its genetic cause is mainly biallelic mutations of the Wolframin endoplasmatic reticulum transmembrane glycoprotein gene Wfs1. These result in increased ER stress, which in turn induces apoptosis and leads to the depletion of the corresponding cells and a loss of their physiological functions. Though diabetes mellitus is mostly treated by insulin, there is still no proven cure for the disease in general. It leads to premature death in affected individuals-usually within the 4th decade of live.
Clinical studies are currently being conducted at various locations worldwide to test a therapy for the disease using various approaches.
As rare diseases in general represent a major challenge for individual clinicians and researchers due to the rarity of diagnosis, the lack of evidence and of value of existing research, international cooperation, coordination and networking leading to an alignment of different stakeholders is necessary to support patients and increase knowledge about these diseases, like wolfram syndrome.
ENDO-ERN and EURRECA are two EU-funded networks that aim to promote knowledge sharing, education and research on rare endocrine diseases.
Wolfram 综合征是一种非常罕见的遗传性疾病，可导致糖尿病、失明、耳聋、尿崩症和进行性脑干退化。受影响患者的神经症状包括共济失调、睡眠呼吸暂停、膀胱控制丧失、吞咽困难、味觉丧失以及进行性神经退行性病变的伴随精神症状。其遗传原因主要是 Wolframin 内质网跨膜糖蛋白基因 Wfs1 的双等位基因突变。这会导致内质网应激增加，进而诱导细胞凋亡，导致相应细胞耗竭及其生理功能丧失。尽管糖尿病大多通过胰岛素治疗，但总体上仍没有针对该疾病的有效治疗方法。受影响个体通常在生命的第四个十年内死亡。
目前正在全球各地的多个地点进行临床试验，以使用各种方法测试该疾病的治疗方法。
一般来说，由于诊断罕见、现有研究证据和价值不足，罕见疾病对个体临床医生和研究人员构成重大挑战，因此需要国际合作、协调和网络联系，以支持患者并增加对这些疾病（如 Wolfram 综合征）的了解。
ENDO-ERN 和 EURRECA 是两个欧盟资助的网络，旨在促进对罕见内分泌疾病的知识共享、教育和研究。
