Review
Version 1
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Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease
Version 1
: Received: 6 July 2024 / Approved: 8 July 2024 / Online: 8 July 2024 (10:01:16 CEST)
How to cite: Caruso, V.; Raia, A.; Rigoli, L. Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease. Preprints 2024, 2024070604. https://doi.org/10.20944/preprints202407.0604.v1 Caruso, V.; Raia, A.; Rigoli, L. Wolfram Syndrome 1: A Neuropsychiatric Perspective on a Rare Disease. Preprints 2024, 2024070604. https://doi.org/10.20944/preprints202407.0604.v1
Abstract
Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients.
Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system.
WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, it is critical to provide genetic counseling to the patient's relatives in order to reduce the risk of transmitting WS1. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients.
This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric diseases commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.
Keywords
Wolfram syndrome 1; WFS1 gene; neuropsichiatric disorders; new findings in Wolfram syndrome 1.
Subject
Medicine and Pharmacology, Psychiatry and Mental Health
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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