Association of optic atrophy and type 1 diabetes: clinical hallmarks for the diagnosis of Wolfram syndrome

Pedroso, José Luiz; Lucato, Leandro Tavares; Kok, Fernando; Sallum, Juliana Maria Ferraz; Barsottini, Orlando Graziani Póvoas; Oliveira, Acary Souza Bullé

doi:10.1590/0004-282x20150021

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…The first clinical signs of WFS are diabetes mellitus (DM) and optic atrophy (OA). Typically, the onset of insulin-dependent DM precedes the diagnosis of OA, by a margin of 4 years on average [ 5 – 7 ]. Other features of the syndrome, which develop as the patient gets older, are: progressive blindness and deafness, diabetes insipidus, urodynamic and endocrinological disorders, and psychiatric and neurological abnormalities [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

et al. 2017

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AimsWolfram syndrome (WFS) is a recessively inherited monogenic form of diabetes coexisting with optic atrophy and neurodegenerative disorders with no currently recognized markers of disease progression. The aim of the study was to evaluate retinal parameters by using optical coherence tomography (OCT) in WFS patients after 2 years of follow-up and analysis of the parameters in relation to visual acuity.MethodsOCT parameters and visual acuity were measured in 12 WFS patients and 31 individuals with type 1 diabetes.ResultsTotal thickness of the retinal nerve fiber layer (RNFL), average retinal thickness and total retinal volume decreased in comparison with previous OCT examination. Significant decreases were noted for RNFL (average difference −17.92 µm 95% CI −30.74 to −0.10; p = 0.0157), macular average thickness (average difference −5.38 µm 95% CI −10.63 to −2.36; p = 0.0067) and total retinal volume (average difference −0.15 mm3 95% CI −0.30 to −0.07; p = 0.0070). Central thickness remained unchanged (average difference 1.5 µm 95% CI −7.61 to 10.61; p = 0.71). Visual acuity of WFS patients showed a strong negative correlation with diabetes duration (R = −0.82; p = 0.0010). After division of WFS patients into two groups (with low-vision and blind patients), all OCT parameters except for the RNFL value were lower in blind WFS patients.ConclusionsOCT measures structural parameters and can precede visual acuity loss. The OCT study in WFS patients should be performed longitudinally, and serial retinal examinations may be helpful as a potential end point for future clinical trials.

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Section: Introductionmentioning

confidence: 99%

Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

et al. 2017

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Deafness and Vestibulopathy in Cerebellar Diseases: a Practical Approach

et al. 2019

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WFS1 Gene–associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India

Chapla

Johnson

Korula

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge. Objective With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes. Methods This case series of 11 patients who were positive for WFS1 variants were identified with next-generation sequencing (NGS)–based screening of 17 genemonogenic diabetes panel. These results were further confirmed with Sanger sequencing. Results 9 out of 11 patients were homozygous for pathogenic/likely pathogenic variants in the WFS1 gene. Interestingly, 3 of these probands were positive for the novel WFS1 (NM_006005.3): c.1107_1108insA (p.Ala370Serfs*173) variant, and haplotype analysis suggested a founder effect in 3 families from Southern India. Additionally, we identified 2 patients with young-onset diabetes who were heterozygous for a likely pathogenic variant or a variant of uncertain significance in the WFS1 gene. Conclusion These results project the need for NGS-based parallel multigene testing as a tool for early diagnosis of WFS and identify heterozygous WFS1 variants implicated in young-onset diabetes.

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Association of optic atrophy and type 1 diabetes: clinical hallmarks for the diagnosis of Wolfram syndrome

Cited by 3 publications

References 5 publications

Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

Retinal thickness as a marker of disease progression in longitudinal observation of patients with Wolfram syndrome

Deafness and Vestibulopathy in Cerebellar Diseases: a Practical Approach

WFS1 Gene–associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India

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