TY - JOUR
T1 - Two Cases of Wolfram Syndrome Who Were Initially Diagnosed With Type 1 Diabetes
AU - Silvestri, Francesca
AU - Tromba, Valeria
AU - Costantino, Francesco
AU - Palaniappan, Nila
AU - Urano, Fumihiko
N1 - Funding Information:
F.U. thanks philanthropic supports from the Silberman Fund, the Ellie White Foundation for the Rare Genetic Disorders, the Snow Foundation, the Unravel Wolfram Syndrome Fund, the Stowe Fund, the Eye Hope Foundation , the Feiock Fund, Ontario Wolfram League, Associazione Gentian-Sindrome di Wolfram Italia, Alianza de Familias Afectadas por el Sindrome Wolfram Spain, Wolfram Syndrome UK, and Association Syndrome de Wolfram France. F.U. also thanks all members of the Washington University Wolfram Syndrome Study, Research Clinic, and WFS1 Clinic at the Washington University Medical Center for their support ( https://wolframsyndrome.wustl.edu ) and all participants in the Wolfram Syndrome International Registry and Clinical Study, Research Clinic, and Clinical Trials for their time and efforts.
Funding Information:
F.U. thanks philanthropic supports from the Silberman Fund, the Ellie White Foundation for the Rare Genetic Disorders, the Snow Foundation, the Unravel Wolfram Syndrome Fund, the Stowe Fund, the Eye Hope Foundation, the Feiock Fund, Ontario Wolfram League, Associazione Gentian-Sindrome di Wolfram Italia, Alianza de Familias Afectadas por el Sindrome Wolfram Spain, Wolfram Syndrome UK, and Association Syndrome de Wolfram France. F.U. also thanks all members of the Washington University Wolfram Syndrome Study, Research Clinic, and WFS1 Clinic at the Washington University Medical Center for their support (https://wolframsyndrome.wustl.edu) and all participants in the Wolfram Syndrome International Registry and Clinical Study, Research Clinic, and Clinical Trials for their time and efforts. F.U. received research funds from Eli Lilly, Ono Pharmaceutical, and Amarantus BioScience for the development of MANF-based regenerative therapy for Wolfram syndrome, optic nerve atrophy, and diabetes. F.U. is an inventor of 3 patents related to the treatment of Wolfram syndrome, SOLUBLE MANF IN PANCREATIC BETA CELL DISORDERS (US 9,891,231) and TREATMENT FOR WOLFRAM SYNDROME AND OTHER ER STRESS DISORDERS (US 10,441,574 and US 10,695,324). F.U. is a Founder and President of CURE4WOLFRAM, INC. F.S. V.T. F.C. and N.P. have no multiplicity of interest to disclose.
Publisher Copyright:
© 2022 AACE
PY - 2022
Y1 - 2022
N2 - Objective: 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. Case Report: 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. Discussion: 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. Conclusion: 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.
AB - Objective: 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. Case Report: 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. Discussion: 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. Conclusion: 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.
KW - Wolfram syndrome
KW - diabetes mellitus
KW - endoplasmic reticulum stress
KW - monogenic diabetes genetic testing
KW - optic nerve atrophy
UR - http://www.scopus.com/inward/record.url?scp=85123886708&partnerID=8YFLogxK
U2 - 10.1016/j.aace.2022.01.001
DO - 10.1016/j.aace.2022.01.001
M3 - Article
AN - SCOPUS:85123886708
JO - AACE Clinical Case Reports
JF - AACE Clinical Case Reports
SN - 2376-0605
ER -