Silvestri Francesca, Tromba Valeria, Costantino Francesco, Palaniappan Nila, Urano Fumihiko
Department of Pediatric Diabetology, "Sapienza" University of Rome, Italy.
Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri.
AACE Clin Case Rep. 2022 Jan 12;8(3):128-130. doi: 10.1016/j.aace.2022.01.001. eCollection 2022 May-Jun.
Early diagnosis of syndromic monogenic diabetes allows for proper management and can lead to improved quality of life in the long term. This report aimed to describe 2 genetically confirmed cases of Wolfram syndrome, a rare endoplasmic reticulum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration.
A 16-year-old Caucasian male patient and a 25-year-old Caucasian female patient with a history of diabetes mellitus and optic nerve atrophy presented at our medical center. Both patients were initially diagnosed with type 1 diabetes but negative for islet autoantibodies. Their body mass indexes were under 25 at the diagnosis. Their history and presentation were highly suspicious for Wolfram syndrome.
The genetic tests revealed a known Wolfram syndrome 1 (WFS1) pathogenic variant (homozygous) in the 16-year-old male patient and 2 known WFS1 pathogenic variants (compound heterozygous) in the 25-year-old female patient with diabetes mellitus and optic nerve atrophy, confirming the diagnosis of Wolfram syndrome. The first patient had a moderate form, and the second patient had a milder form of Wolfram syndrome.
Providers should consider monogenic diabetes genetic testing, including WFS1 gene, for patients with early-onset diabetes who are negative for islet autoantibodies and lean. Two patients described in this article could have been diagnosed with Wolfram syndrome before they developed optic nerve atrophy. Genetic testing is a valuable tool for the early detection of Wolfram syndrome, which leads to proper management and improved quality of life in patients with this rare medical condition.
综合征性单基因糖尿病的早期诊断有助于进行恰当管理，并能长期改善生活质量。本报告旨在描述2例经基因确诊的沃夫勒姆综合征病例，这是一种罕见的内质网疾病，其特征为胰岛素依赖型糖尿病、视神经萎缩和进行性神经退行性变。
一名16岁的白种男性患者和一名25岁的白种女性患者因糖尿病和视神经萎缩病史前来我院就诊。两名患者最初均被诊断为1型糖尿病，但胰岛自身抗体检测呈阴性。诊断时他们的体重指数均低于25。他们的病史和临床表现高度怀疑为沃夫勒姆综合征。
基因检测显示，16岁男性患者存在一个已知的沃夫勒姆综合征1型（WFS1）致病变异（纯合子），25岁患有糖尿病和视神经萎缩的女性患者存在2个已知的WFS1致病变异（复合杂合子），从而确诊为沃夫勒姆综合征。首例患者为中度形式，第二例患者为轻度沃夫勒姆综合征。
对于胰岛自身抗体阴性且体型偏瘦的早发型糖尿病患者，医疗服务提供者应考虑进行单基因糖尿病基因检测，包括检测WFS1基因。本文描述的两名患者在出现视神经萎缩之前就可以被诊断为沃夫勒姆综合征。基因检测是早期发现沃夫勒姆综合征的一项有价值的工具，有助于对这种罕见疾病患者进行恰当管理并改善其生活质量。
