Efficacy of GLP-1 Agonist Therapy in Autosomal Dominant WFS1-Related Disorder: A Case Report

2020 ◽  
pp. 1-6
Author(s):  
Kevin J. Scully ◽  
Joseph I. Wolfsdorf
Keyword(s):  
Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Neurodegenerative Disorder ◽  
Low Frequency ◽  
Sensorineural Deafness ◽  
Indirect Evidence ◽  
Wolfram Syndrome ◽  
Related Disorder ◽  
History Of ◽  
Congenital Strabismus

<b><i>Background:</i></b> Wolfram syndrome is a rare neurodegenerative disorder, characterized by the presence of diabetes insipidus, diabetes mellitus, optic atrophy, and sensorineural deafness. The majority of cases are due to autosomal recessive biallelic variants in the <i>WFS1</i> gene; however, pathogenic autosomal dominant (AD) mutations have also been described. Glucagon-like peptide (GLP-1) agonists have been studied in both animal models and humans with classic Wolfram syndrome. <b><i>Case:</i></b> We present a 15-year-old female with a personal and family history of congenital strabismus, bilateral cataracts, low-frequency sensorineural hearing loss, and diabetes mellitus. Trio whole exome sequencing revealed a previously unknown maternally inherited heterozygous variant in exon 8 of the <i>WFS1</i> gene c.2605_2616del12 <i>p</i>.Ser869_His872del, leading to the diagnosis of AD WFS1-related disorder. Treatment with a GLP-1 agonist resulted in marked improvement in glycemic control and discontinuation of insulin therapy. This patient’s response to a GLP-1 agonist provides suggestive indirect evidence for a role of WFS1 on β-cell endoplasmic reticulum stress and suggests that treatment with a GLP-1 agonist should be considered in patients with dominant forms of WS.

scholarly journals Diabetes Mellitus and Optic Atrophy: A Study of Wolfram Syndrome in the Lebanese Population

2004 ◽  
Vol 89 (4) ◽  
pp. 1656-1661 ◽  
Author(s):  
R. Medlej ◽  
J. Wasson ◽  
P. Baz ◽  
S. Azar ◽  
I. Salti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Insipidus ◽  
Optic Atrophy ◽  
Neurodegenerative Disorder ◽  
Sensorineural Deafness ◽  
Microvascular Disease ◽  
Insulin Dependent Diabetes Mellitus ◽  
Wolfram Syndrome ◽  
Dependent Diabetes Mellitus ◽  
Number Of Patients

Abstract Wolfram syndrome (WFS) is a rare hereditary neurodegenerative disorder also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). WFS seems to be a heterogeneous disease that has not yet been fully characterized in terms of clinical features and pathophysiological mechanisms because the number of patients in most series was small. In this study we describe 31 Lebanese WFS patients belonging to 17 families; this, to our knowledge, is the largest number of patients reported in one series so far. Criteria for diagnosis of WFS were the presence of insulin-dependent diabetes mellitus and optic atrophy unexplained by any other disease. Central diabetes insipidus was found in 87% of the patients, and sensorineural deafness confirmed by audiograms was present in 64.5%. Other less frequent features included neurological and psychiatric abnormalities, urodynamic abnormalities, limited joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotropic hypogonadism in males, and diabetic microvascular disease. New features, not reported in previous descriptions, such as heart malformations and anterior pituitary dysfunction, were recognized in some of the patients and participated in the morbidity and mortality of the disease. Genetic analysis revealed WFS1 gene mutations in three families (23.5%), whereas no abnormalities were detected in mitochondrial DNA. In conclusion, WFS is a devastating disease for the patients and their families. More information about WFS will lead to a better understanding of this disease and hopefully to improvement in means of its prevention and treatment.

A mutation in Wolfram syndrome type 1 gene in a Japanese family with autosomal dominant low-frequency sensorineural hearing loss

2005 ◽  
Vol 125 (11) ◽  
pp. 1189-1194 ◽  
Author(s):  
Yoshihiro Noguchi ◽  
Takatoshi Yashima ◽  
Akio Hatanaka ◽  
Masamichi Uzawa ◽  
Michio Yasunami ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Autosomal Dominant ◽  
Low Frequency ◽  
Wolfram Syndrome ◽  
Sensorineural Hearing ◽  
Syndrome Type ◽  
Japanese Family

scholarly journals HDR Syndrome Accompanying Type 1 Diabetes Mellitus and Hypopituitarism

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Mustafa Can ◽  
Feridun Karakurt ◽  
Muhammed Kocabas ◽  
İlker Cordan ◽  
Melia Karakose ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Sensorineural Deafness ◽  
Renal Dysplasia ◽  
Autosomal Dominant Disorder ◽  
Hdr Syndrome

HDR (Hypoparathyroidism, Deafness, and Renal Dysplasia) syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal disease. Approximately 65% of patients with HDR syndrome have all three of these features, while others have different combinations of these features. We aimed to present a case with primary hypoparathyroidism, hearing loss, and nondiabetic chronic kidney disease and diagnosed as HDR syndrome while being followed up for type 1 diabetes mellitus and hypopituitarism.

scholarly journals GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kadri Seppa ◽  
Maarja Toots ◽  
Riin Reimets ◽  
Toomas Jagomäe ◽  
Tuuliki Koppel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Optic Nerve ◽  
Rat Model ◽  
Receptor Agonist ◽  
Neurodegenerative Disorder ◽  
Ganglion Cells ◽  
Neuroprotective Effect ◽  
Wolfram Syndrome ◽  
Retinal Ganglion ◽  
Knock Out

Abstract Wolfram syndrome (WS) is a rare neurodegenerative disorder that is mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown a promising anti-diabetic effect in WS treatment in both animal models and in human patients. Since previous research has tended to focus on investigation of the WS first symptom, diabetes mellitus, the aim of the present study was to examine liraglutide effect on WS-associated neurodegeneration. We took 9-month-old Wfs1 knock-out (KO) animals that already had developed glucose intolerance and treated them with liraglutide for 6 months. Our research results indicate that 6-month liraglutide treatment reduced neuroinflammation and ameliorated endoplasmic reticulum (ER) stress in the inferior olive of the aged WS rat model. Liraglutide treatment also protected retinal ganglion cells from cell death and optic nerve axons from degeneration. According to this, the results of the present study provide novel insight that GLP-1 receptor agonist liraglutide has a neuroprotective effect in the WS rat model.

scholarly journals Posttransplant Tacrolimus-Induced Diabetic Ketoacidosis: Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Zaid Ammari ◽  
Stella C. Pak ◽  
Mohammed Ruzieh ◽  
Osama Dasa ◽  
Abhinav Tiwari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Adverse Event ◽  
Kidney Transplantation ◽  
Diabetic Ketoacidosis ◽  
Autosomal Dominant ◽  
Immunosuppressive Regimen ◽  
Review Of The Literature ◽  
Polycystic Kidney ◽  
History Of ◽  
Autosomal Dominant Polycystic Kidney

Diabetic ketoacidosis (DKA) in patients receiving tacrolimus as part of their immunosuppressive regimen is a rarely reported adverse event. We report a patient with autosomal dominant polycystic kidney disease (ADPKD) and no known history of diabetes mellitus who presented with DKA, 3 months after kidney transplantation.

scholarly journals Clinical and genetic analysis of two wolfram syndrome families with high occurrence of wolfram syndrome and diabetes type II: a case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Sobhani ◽  
Mohammad Amin Tabatabaiefar ◽  
Soudeh Ghafouri-Fard ◽  
Asadollah Rajab ◽  
Asal Hojjat ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Neurodegenerative Disorder ◽  
Autoimmune Diabetes ◽  
Wolfram Syndrome ◽  
Clinical Diagnostics ◽  
Genetic Linkage Analysis ◽  
Diabetes Type Ii ◽  
Pathogenic Variants ◽  
High Prevalence ◽  
Syndromic Hearing Loss

Abstract Background Mutations of the WFS1 gene are responsible for most cases of Wolfram syndrome (WS), a rare, recessively inherited neurodegenerative disorder characterized by juvenile-onset non-autoimmune diabetes mellitus and optic atrophy. Variants of WFS1 are also associated with non-syndromic hearing loss and type-2 diabetes mellitus (T2DM). Our study adds to literature significant associations between WS and T2DM. Case presentation In this study, we analyzed the clinical and genetic data of two families with high prevalence of WS and T2DM. Genetic linkage analysis and DNA sequencing were exploited to identify pathogenic variants. One novel pathogenic variant (c.2243-2244insC) and one known pathogenic (c.1232_1233delCT) (frameshift) variant were identified in exon eight of WFS1 gene. Conclusions The mutational and phenotypic spectrum of WS is broadened by our report of novel WFS1 mutation. Our results reveal the value of molecular analysis of WFS1 in the improvement of clinical diagnostics for WS. This study also confirms the role of WFS1 in T2DM.

scholarly journals The importance of multidisciplinary care of patients with Wolfram

2018 ◽  
Vol 1 (2) ◽  
pp. 01-03
Author(s):  
Rebecca A Dennison
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Insipidus ◽  
Optic Atrophy ◽  
Severe Hypoglycemia ◽  
Multidisciplinary Care ◽  
Wolfram Syndrome ◽  
Continuous Glucose Monitor ◽  
Hypoglycemia Unawareness ◽  
History Of

Background: Wolfram syndrome is a genetic condition, which is typically inherited in autosomal recessive fashion, characterized by the combination of diabetes mellitus and optic atrophy. It is along a spectrum which encompasses DIDMOAD (Diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Profound hypoglycemic unawareness can be seen in this condition but is not commonly described as an associated feature in the literature. Case report: A 16 year old female with history of presumed type 1 diabetes presented to urology clinic with urinary incontinence. She was found to have profound dilation of the bladder and was admitted for bladder decompression. During the course of admission she was found to also have diabetes insipidus and optic atrophy. She had several severe hypoglycemic episodes with profound hypoglycemia unawareness during this admission. Genetic testing for Wolfram syndrome was positive. As an outpatient she was placed on a continuous glucose monitor to help manage her hypoglycemia. Addtionally, psychiatric support to manage her associated depression was an important aspect of her therapy. As her depression improved so did her ability to comply with the necessary therapies. Conclusions: Wolfram syndrome is a rare syndrome that has been well described. However, patients with this syndrome have frequent hypoglycemia unawareness and severe hypoglycemia likely related to the neurologic deterioration that occurs at the molecular level in the pathogenesis of Wolfram syndrome. Strategies must be put in to place to help prevent and quickly treat these hypoglycemic events.

scholarly journals Wolfram Syndrome in a Family with Variable Expression

2001 ◽  
Vol 44 (3) ◽  
pp. 115-118 ◽  
Author(s):  
Abdurrahman Kadayifci ◽  
Yalcin Kepekci ◽  
Yavuz Coskun ◽  
Ying Huang
Keyword(s):  
Autosomal Recessive ◽  
Dna Analysis ◽  
Neurodegenerative Disorder ◽  
Sensorineural Deafness ◽  
Autosomal Recessive Inheritance ◽  
Wolfram Syndrome ◽  
Carrier State ◽  
Variable Expression ◽  
Phenotypic Variations ◽  
Characteristic Features

Wolfram syndrome is a rare neurodegenerative disorder with autosomal recessive inheritance. The main characteristic features of this disorder are diabetes mellitus and optic atrophy. However, diabetes insipidus, sensorineural deafness, renal tract and neurologic abnormalities are seen in majority of patients. In this study, we describe a family in which two members had the main features of the syndrome while a third sibling had only sensorineural deafness. DNA analysis revealed that the fully affected siblings were homozygote for a pointmutation on chromosome 4p whereas the third sibling with deafness was a heterozygote carrier for the same mutation. The characteristics of disease and phenotypic variations that possibly related to heterozygote carrier state were discussed.

scholarly journals Wolfram syndrome: a case report with severe polyuria and secondary urological abnormalities

2021 ◽  
Vol 8 (4) ◽  
pp. 759
Author(s):  
Niranjan kumbara Hunasagatta Omkarappa ◽  
Prashanth Siddaiah ◽  
Shalini Sankalapura Rangaswamy ◽  
Ramu Anjanaiah ◽  
Devika Chennakeshava ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Case Report ◽  
Diabetes Insipidus ◽  
Type 1 Diabetes Mellitus ◽  
Optic Atrophy ◽  
Sensorineural Deafness ◽  
Wolfram Syndrome ◽  
Dependent Diabetes Mellitus

Wolfram syndrome is the condition characterized by juvenile onset diabetes mellitus and optic atrophy, which is also known as DIDMOAD. Classical Wolfram syndrome is a rare autosomal recessive disorder caused by mutations in WFS1, a gene involved in endoplasmic reticulum and mitochondrial function. Patients present with type 1 diabetes mellitus followed by optic atrophy in the first decade, diabetes insipidus and sensorineural deafness in the second decade, dilated renal outflow tracts as early as in the third decade, and various neurological abnormalities in the early fourth decade. We describe a case report of 14-year-old male child diagnosed as wolfram syndrome with type 1 diabetes mellitus, diabetes insipidus, deafness, optic atrophy and severe urological abnormalities. Patients who present with early onset insulin-dependent diabetes mellitus and optic atrophy together should be evaluated with respect to Wolfram Syndrome. If a patient, who is a known case of diabetes mellitus, presents with persistent polyuria or neurogenic bladder despite good glycemic control, suspicion of wolfram syndrome and further evaluation regarding the same must be made. Recognizing and timely management of this condition will help to improve the quality of life in the patient.

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