Wolfram Syndrome 1: From Genetics to Therapy

Luciana Rigoli, Valerio Caruso, Giuseppina Salzano and Fortunato Lombardo
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Luciana Rigoli: Department of Human Pathology of Adulthood and Childhood G. Barresi, University of Messina, 98125 Messina, Italy
Valerio Caruso: Psychiatry 2 Unit, Clinical and Experimental Medicine Department, University of Pisa, 56126 Pisa, Italy
Giuseppina Salzano: Department of Human Pathology of Adulthood and Childhood G. Barresi, University of Messina, 98125 Messina, Italy
Fortunato Lombardo: Department of Human Pathology of Adulthood and Childhood G. Barresi, University of Messina, 98125 Messina, Italy

IJERPH, 2022, vol. 19, issue 6, 1-18

Abstract: Wolfram syndrome 1 (WS1) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. It is characterized by diabetes insipidus (DI), diabetes mellitus (DM), optic atrophy (OA), and sensorineural hearing loss (D) (DIDMOAD). The clinical picture may be complicated by other symptoms, such as urinary tract, endocrinological, psychiatric, and neurological abnormalities. WS1 is caused by mutations in the WFS1 gene located on chromosome 4p16 that encodes a transmembrane protein named wolframin. Many studies have shown that wolframin regulates some mechanisms of ER calcium homeostasis and therefore plays a role in cellular apoptosis. More than 200 mutations are responsible for WS1. However, abnormal phenotypes of WS with or without DM, inherited in an autosomal dominant mode and associated with one or more WFS1 mutations, have been found. Furthermore, recessive Wolfram-like disease without DM has been described. The prognosis of WS1 is poor, and the death occurs prematurely. Although there are no therapies that can slow or stop WS1, a careful clinical monitoring can help patients during the rapid progression of the disease, thus improving their quality of life. In this review, we describe natural history and etiology of WS1 and suggest criteria for a most pertinent approach to the diagnosis and clinical follow up. We also describe the hallmarks of new therapies for WS1.

Keywords: Wolfram syndrome 1; WFS1; diabetes mellitus; optic atrophy; diabetes insipidus; sensorineural deafness; new therapies for Wolfram syndrome 1 (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

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