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Erschienen in: Endocrine 2/2020

29.04.2020 | Original Article

Wolfram syndrome: clinical and genetic profiling of a cohort from a tertiary care centre with characterization of the primary gonadal failure

verfasst von: Liza Das, Ashutosh Rai, Ravimohan Mavuduru, Kim Vaiphei, Akhilesh Sharma, Vishali Gupta, Sanjay Kumar Bhadada, Sailesh Lodha, Naresh Panda, Anil Bhansali, Paramjeet Singh, Pinaki Dutta

Erschienen in: Endocrine | Ausgabe 2/2020

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Abstract

Background

Wolfram syndrome (WFS) is a rare, monogenic neurodegenerative syndrome characterised by insulin requiring non-autoimmune diabetes mellitus (DM) and optic atrophy which are usually the earliest and commonest manifestations. However, there are other features which are under-recognized, adding to morbidity and premature mortality in these patients.

Methods

Five patients (three males, two females) with genetically confirmed WFS at a single tertiary care centre were prospectively followed up. Their symptomatology, clinical profile, genetic analysis and radiology were analyzed. Multidisciplinary approach was used for comprehensive clinical care of this cohort. Patients with primary gonadal failure were subjected to biopsy and immunohistochemistry (IHC) for wolframin was performed.

Results

DM was the earliest presenting manifestation at 6.2 ± 1.3 years followed by optic atrophy at 10.4 ± 2.3 years, diabetes insipidus at 12 ± 2.1 years and deafness at 12.8 ± 2.1 years. All patients were autoantibody negative with low C-peptide(<0.6 ng/ml). Hypoglycemic episodes were frequent (upto 60%) but there was no instance of diabetic ketoacidosis. Optic atrophy was present alongwith proliferative diabetic retinopathy and cataract in 40%. Uncommon manifestations included neuropsychiatric features, parasuicide, cystopathy, brainstem atrophy and hypergonadotropic hypogonadism only in adult males (n = 2). Testicular biopsy revealed partly hyalinised seminiferous tubules and prominence of Leydig cells. IHC confirmed the presence of mutated wolframin, which was not significantly different from normal testis specimen on protein quantification.

Conclusions

WFS requires a multidisciplinary approach with special emphasis on early diagnosis and management of other endocrine and non-endocrine features so as to improve long-term outcomes. Gonadal functions need periodic assessment, especially in adult males.
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Metadaten
Titel
Wolfram syndrome: clinical and genetic profiling of a cohort from a tertiary care centre with characterization of the primary gonadal failure
verfasst von
Liza Das
Ashutosh Rai
Ravimohan Mavuduru
Kim Vaiphei
Akhilesh Sharma
Vishali Gupta
Sanjay Kumar Bhadada
Sailesh Lodha
Naresh Panda
Anil Bhansali
Paramjeet Singh
Pinaki Dutta
Publikationsdatum
29.04.2020
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 2/2020
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-020-02320-6

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