Publication: cureus.com | Publication Date: 6 May 2025
Authors: Nadia Echcharii, Nabila Chekhlabi, Amal Haoudar, Nezha Dini
Wolfram syndrome (WS) is a rare, autosomal recessive neurodegenerative disorder characterized by progressive multisystemic involvement, including diabetes mellitus, optic atrophy, diabetes insipidus, sensorineural hearing loss, and urological dysfunction. While diabetes mellitus is typically the first clinical sign, atypical presentations can delay the diagnosis.
Publication: cureus.com | Publication Date: 25 October 2025
Authors: Tej P. Shah, Richard Sidlow, Prem K. Sah
Wolfram syndrome is a rare autosomal recessive disorder characterized by diabetes mellitus, optic atrophy, and progressive neurodegeneration, often summarized by the acronym DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We report a 27-year-old male with a history of diabetes mellitus, progressive visual loss leading to blindness, and bilateral sensorineural hearing loss. His family history was notable for diabetes-related mortalities and visual impairment in multiple members of the family. Clinical evaluation showed uncontrolled blood glucose level, optic atrophy, and high-frequency sensorineural hearing loss. A clinical diagnosis of Wolfram syndrome was made using the Euro-Wolfram, Alström, and Bardet-Biedl (WABB) criteria. Wolfram syndrome should be suspected in young patients with early-onset diabetes mellitus and visual or hearing impairment. This case report highlights the role of timely multidisciplinary management in preventing disease-related complications.
Publication: frontiersin.org | Publication Date: 14 October 2025
Authors: Justin Simo, Heather M. Lugar, Elka Miller, Adi Wilf-Yarkoni, Yael Goldberg, Ayça Kocaağa, Shoichi Ito, Sirio Cocozza, Giulio Frontino, Cristina Baldoli, Aziz Benbachir, Catherine Ashton, Guy Rouleau, Tamara Hershey, Yann Nadjar, Roberta La Piana
Wolfram syndrome (WFS) is a genetic disorder mainly caused by pathogenic variants in the WFS1 gene. It is characterized clinically by optic atrophy (OA), diabetes mellitus (DM), sensorineural hearing loss (SNHL), diabetes insipidus (DI), and variable neurological/psychiatric symptoms. WFS typically manifests before age 20 and progresses into adulthood. Classical neuroradiological features include cerebellar and/or brainstem atrophy as well as white matter abnormalities ranging from small, ovoid lesions to diffuse, symmetrical changes along the visual pathway. Following the identification of multifocal, progressive white matter abnormalities that prompted the consideration of multiple sclerosis (MS) in two molecularly confirmed WFS subjects, we sought to verify whether MS-like lesions constitute a novel WFS-associated MRI pattern.
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Publication: onlinelibrary.wiley.com | Publication Date: 29 April 2025
Authors: Ibrar Rafique, Asif Mir, Natalija Popovic, Alix Vanpoperinghe, Muhammad Arif Nadeem Saqib, Asher Fawwad, Abdul Basit, Muhammad Naeem, Constantin Polychronakos, Angeliki Makri
We examined 68 Pakistani patients with young onset diabetes and found a surprisingly high rate (4/68) of non-syndromic WFS1 diabetes, a recently described recessive condition. This frequency far exceeds the prevalence of the fully expressed syndrome, probing the effect of high consanguinity on the risk of non-syndromic WFS1 diabetes.
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Publication: onlinelibrary.wiley.com | Publication Date: 29 April 2025
Authors: J. Rohayem and O. Cunningham
WFS1 spectrum disorder, also known as Wolfram syndrome (WS) is an ultra-rare (<1:500,000; ORPHA: 3463) monogenic (OMIM #222300) progressive neuroendocrine and neurodegenerative disorder, characterised by early-onset insulin-dependent diabetes, optic atrophy, central diabetes insipidus and sensi-neuronal deafness. It is caused predominantly by bi-allelic mutations in the WFS1 gene and exceptionally in the WFS2-gene. There is very limited published data on gonadal function in young people with WS. Expansion of the phenotype has previously included suggestions of abnormalities in puberty in adolescents with (WS) but with little detail.
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Publication: biomedcentral.com | Publication Date: 06 March 2025
Authors: Jagomäe, T., Velling, S., Tikva, T.B. et al.
Wolfram syndrome (WS) is a rare autosomal disorder caused by WFS1 gene mutations, currently lacking approved treatments. Preclinical and clinical reports suggest that diabetes medications, such as glucagon-like peptide-1 receptor agonist (GLP1-RA), slow WS-related diabetes and neurodegeneration, improving patient outcomes.
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Publication: science.org | Publication Date: 2025
Authors: Kikuko Amo-Shiinoki et al.
Insulin-dependent diabetes in patients with Wolfram syndrome (WS; OMIM 222300) has been linked to endoplasmic reticulum (ER) stress caused by WFS1 gene mutations. However, the pathological process of ER stress–associated β cell failure remains to be fully elucidated. Our results indicate loss of β cell lineage and subsequent dedifferentiation as the mechanisms underlying functional and mass deficits in WS.
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Publication: ncbi.nlm.nih.gov | Publication Date: September 30, 2014
Authors: Zatyka, M., Da Silva Xavier, G., Bellomo, E. A., Leadbeater, W., Astuti, D., Smith, J., Michelangeli, F., Rutter, G. A., & Barrett, T. G.
Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. Read more
Publication: jbc.org | Publication Date: December 2003
Authors: Abdullah A. Osman, Mitsuyoshi Saito, Carol Makepeace, M. Alan Permutt, Paul Schlesinger, Mike Mueckler
Wolfram syndrome is an autosomal recessive neuro-degenerative disorder associated with juvenile onset non-autoimmune diabetes mellitus and progressive optic atrophy. The disease has been attributed to mutations in the WFS1 gene, which codes for a protein predicted to possess 9–10 transmembrane segments. Little is known concerning the function of the WFS1 protein (wolframin). Read more
Publication: ncbi.nlm.nih.gov | Publication Date: 2016
Authors: Fumihiko Urano
Wolfram syndrome is a rare genetic disorder characterized by juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration. Although there are currently no effective treatments that can delay or reverse the progression of Wolfram syndrome, the use of careful clinical monitoring and supportive care can help relieve the suffering of patients and improve their quality of life. Read more
The Snow Foundation is a collective voice for Wolfram syndrome patients, working towards a cure for Wolfram syndrome and developing novel therapies for diabetes, vision loss, hearing loss and neurodegeneration.
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