Two cases of Wolfram syndrome who were initially diagnosed with type 1 diabetes

Abstract: Hypothesis About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. Methods As proof of principle, we examined by exome sequencing families with two or more children, recruited by the Type 1 Diabetes Genetics Consortium and selected for negativity for two autoantibodies and absence of risk HLA haplotypes. Results We examined 46 families that met the criteria. Of the 17 with an affected parent, seven (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including five with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. Conclusions Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that non-syndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.

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Delayed Recognition of Wolfram Syndrome Frequently Misdiagnosed as Type 1 Diabetes with Early Chronic Complications

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0033-1357160 ◽

2014 ◽

Vol 122 (01) ◽

pp. 35-38 ◽

Cited By ~ 13

Author(s):

A. Zmyslowska ◽

M. Borowiec ◽

P. Fichna ◽

B. Iwaniszewska ◽

L. Majkowska ◽

...

Keyword(s):

Type 1 Diabetes ◽

Wolfram Syndrome ◽

Chronic Complications ◽

Delayed Recognition

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Genetics of monegenic forms of diabetes mellitus

Diabetes Mellitus ◽

10.14341/2072-0351-6246 ◽

2011 ◽

Vol 14 (1) ◽

pp. 20-27 ◽

Cited By ~ 3

Author(s):

Tamara Leonidovna Kuraeva ◽

Lyubov' Iosifovna Zil'berman ◽

Elena Vital'evna Titovich ◽

Valentina Alexandrovna Peterkova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Genetic Counseling ◽

Molecular Biology ◽

Wolfram Syndrome ◽

Rare Occurrence ◽

Genetic Syndromes ◽

Wide Range ◽

Actual Prevalence

It is universally recognized that autoimmune type 1 diabetes mellitus (DM) is not the only form of this disease in children. Increasingly more children andadolescents present with DM2, MODY, and rarer syndromal forms of DM. The actual prevalence of DM other than DM1 in children and adolescentsis unknown but may be estimated at 10%. Despite rare occurrence of genetic syndromes, they collectively account for almost 5% of DM cases amongchildren. The rapid upgrowth of molecular biology opens up a wide range of possibilities for designating various symptom complexes as nosologically selfconsistentforms. New genetic syndromes associated with DM are annually described. It is important both to adequately identify and treat manifestationsand complications of these syndromes in children and to provide relevant medico-genetic counseling and recommendations to the parents.Key words: non-immune diabetes mellitus, MODY, Wolfram syndrome, neonatal, syndromal forms

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The epidemiology and genetic analysis of children with idiopathic type 1 diabetes in the state of Qatar

Journal of the Endocrine Society ◽

10.1210/jendso/bvab131 ◽

2021 ◽

Author(s):

Tasneem Abdel-Karim ◽

Basma Haris ◽

Houda Afyouni ◽

Shayma Mohammed ◽

Amel Khalifa ◽

...

Keyword(s):

Type 1 Diabetes ◽

Wolfram Syndrome ◽

Insulin Requirement ◽

Monogenic Diabetes ◽

C Peptide ◽

Peptide Level ◽

Uncertain Significance ◽

Age Of Diagnosis ◽

History Of

Abstract Background To study the epidemiology, describe the clinical characteristics and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes. Methods Prospective study of type 1 diabetes patients attending Sidra Medicine from 2018-2020. Autoantibodies (GAD65, IAA, IA-2A and ZnT8) measured and genetic testing undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes compared to patients with autoimmune type 1 diabetes. Results 1157 patients had type 1 diabetes of which 63 were antibody negative. Upon genome sequencing, four had MODY, two had Wolfram syndrome, one had H syndrome and three had variants of uncertain significance in MODY genes. 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10-14 years and C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average BMI was in the normal range and 33% of the patients had history of DKA. Conclusions 4% of children have Idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the two groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is not known but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

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