Metabolic Treatment of Wolfram Syndrome.

Dario Iafusco,Alessia Piscopo,Emanuele Miraglia Del Giudice,Stefano Curto,Giovanna Maione,Alda Troncone,Fernanda Iafusco,Gulsum Ozen,Pier Luigi Palma,Nadia Tinto,Veronica Testa,Lucia Boccabella,Antonietta Chianese,Angela Zanfardino,Assunta Serena Rollato,Cristina Mazzaccara,Alessandro Pennarella

doi:10.3390/ijerph19052755

Abstract

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms that occur from childhood to adulthood. Usually, the first clinical sign is non-autoimmune diabetes even if other clinical features (optic subatrophy, neurosensorial deafness, diabetes insipidus) may be present in an early state and may be diagnosed after diabetes’ onset. Prognosis is poor, and the death occurs at the median age of 39 years as a consequence of progressive respiratory impairment, secondary to brain atrophy and neurological failure. The aim of this paper is the description of the metabolic treatment of the WS. We reported the experience of long treatment in patients with this syndrome diagnosed in pediatric age and followed also in adult age. It is known that there is a correlation between metabolic control of diabetes, the onset of other associated symptoms, and the progression of the neurodegenerative alterations. Therefore, a multidisciplinary approach is necessary in order to prevent, treat and carefully monitor all the comorbidities that may occur. An extensive understanding of WS from pathophysiology to novel possible therapy is fundamental and further studies are needed to better manage this devastating disease and to guarantee to patients a better quality of life and a longer life expectancy.

Highlights

Wolfram Syndrome (WS) is a very rare genetic disorder characterized by several symptoms, such as juvenile-onset diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing loss, and neurodegeneration, which appear from childhood to adulthood [1]
Hearing loss can be an associated pathology of suspicion and it is certainly very interesting that the peculiar case that we have described in this paper, of a child who was born with congenital sensorineural deafness for which it was necessary to perform the cochlear implant, and who developed diabetes after only a few years, which allowed him to make the diagnosis of genetic syndrome, confirmed by a genetic analysis
Wolfram Syndrome is a very rare genetic disorder characterised by many symptoms that appear one after the other in succession, from childhood to adulthood

Summary

Introduction

Wolfram Syndrome (WS) is a very rare genetic disorder, autosomal recessive, and characterized by many symptoms (diabetes mellitus, diabetes insipidus, optic atrophy, neurosensorial deafness and neurological signs) that appear in succession from childhood to adulthood [1]. Other clinical features include bladder and bowel dysfunction, peripheral neuropathy, psychiatric and neurological abnormalities

Pathogenesis

Metabolic Features of Wolfram Syndrome

Wolfram Syndrome Treatment by Regenerative and Gene Therapy

Findings

Conclusions