Clinical Peculiarities in a Cohort of Patients with Wolfram Syndrome 1.

Giuseppina Salzano,Stefano Passanisi,Fortunato Lombardo,Luciana Rigoli,Mariella Valenzise,Roberto Chimenz

doi:10.3390/ijerph19010520

Abstract

Wolfram syndrome 1 is a rare, autosomal recessive, neurodegenerative, progressive disorder. Insulin-dependent, non-autoimmune diabetes mellitus and bilateral progressive optic atrophy are both sensitive and specific criteria for clinical diagnosis. The leading cause of death is central respiratory failure resulting from brainstem atrophy. We describe the clinical features of fourteen patients from seven different families followed in our Diabetes Center. The mean age at Wolfram syndrome 1 diagnosis was 12.4 years. Diabetes mellitus was the first clinical manifestation, in all patients. Sensorineural hearing impairment and central diabetes insipidus were present in 85.7% of patients. Other endocrine findings included hypogonadotropic hypogonadism (7.1%), hypergonadotropic hypogonadism (7.1%), and Hashimoto’s thyroiditis (21.4%). Neuropsychiatric disorders were detected in 35.7% of patients, and urogenital tract abnormalities were present in 21.4%. Finally, heart diseases were found in 14.2% of patients. Eight patients (57.1%) died at the mean age of 27.3 years. The most common cause of death was respiratory failure which occurred in six patients. The remaining two died due to end-stage renal failure and myocardial infarction. Our data are superimposable with those reported in the literature in terms of mean age of onset, the clinical course of the disease, and causes of death. The frequency of deafness and diabetes insipidus was higher in our patients. The incidence of urogenital diseases was lower although it led to the death of one patient. Long-term follow-up studies including large patient cohorts are necessary to establish potential genotype-phenotype correlation in order to personalize the most suitable clinical approach for each patient.

Highlights

Introduction published maps and institutional affilAccording to the draft International Classification of Disease (ICD-11), Wolfram syndrome (WS) is defined as a rare, specified form of diabetes mellitus (DM) caused by other genetic syndromes
WS is an autosomal, recessive, progressive neurodegenerative disease characterized by early-onset non-autoimmune insulin-dependent DM and bilateral optic neuropathy (OA), which are the key clinical criteria used to make a diagnosis [1,2]
WS1 is a rare neurodegenerative disease that is still characterized by complex heterogeneous clinical expressivity, poor quality of life, and shortened lifespan

Summary

Introduction

Introduction published maps and institutional affilAccording to the draft International Classification of Disease (ICD-11), Wolfram syndrome (WS) is defined as a rare, specified form of diabetes mellitus (DM) caused by other genetic syndromes. WS is an autosomal, recessive, progressive neurodegenerative disease characterized by early-onset non-autoimmune insulin-dependent DM and bilateral optic neuropathy (OA), which are the key clinical criteria used to make a diagnosis [1,2]. It was first reported by Wolfram and Wagener in 1938. The WFS1 gene maps to chromosome 4p16.1, and consists of eight exons encoding wolframin, which is a pleiotropic transmembrane protein located in the endoplasmic reticulum (ER) with 890 amino acid residues and an apparent molecular mass iations

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