Natural history and clinical characteristics of 50 patients with Wolfram syndrome

Abstract

Purpose

To describe clinical characteristics of diabetes mellitus (DM) in a group of patients with Wolfram Syndrome (WS).

Methods

Descriptive, cross-sectional observational design. The sample consisted of 50 patients diagnosed with WS. Clinical criteria contributing to WS diagnosis were analyzed: diabetes mellitus (DM), optic nerve atrophy (OA), sensorineural deafness, urological and neurological dysfunction, among others. These parameters were assessed according to their presence/absence, age of onset, and various clinical-analytical parameters.

Results

All the patients studied presented DM and OA, with a mean age of onset of 5.4 ± .9 (1–14) years and 9 ± .9 (1–16) years, respectively. The remaining criteria were present with a variable frequency: 77% had diabetes insipidus, 66.7% auditory alterations, 77.8% neurogenic bladder, 61.1% neurological involvement, and 27.8% hypogonadism. A 16.7% of the patients had positive albuminuria (urinary albumin/creatinine ratio > 30 mg/g) and 72.2% had hyporreflexia. There were no significant differences in the age of diagnosis nor of the presence of different pathologies according to sex.

Conclusions

The early presence of a non-autoimmune insulin dependent DM, should alert us of an “infrequent” diabetes syndrome. Wolfram’s presumptive diagnosis could be established if juvenile-onset DM occurs concomitantly with OA, and this visual impairment is not attributable to diabetic retinopathy. Despite the long period of evolution of DM and altered values of HbA1c, the prevalence of microvascular complications in the sample are low.

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Acknowledgements

We sincerely thank the patients and families of the Association for Research and Help for Wolfram Syndrome who have agreed to participate in this study. To Dr. Timothy G. Barrett for his invaluable contributions in the present manuscript, to the professionals that make up the Multidisciplinary Team of Wolfram Syndrome (Mónica Ruano Garcia (MF y C), Luisa M. Botella Cubells (Inv. genética), Luz María Martín Egea (psicóloga), Fernando Sánchez García (pediatría) Maria Alharilla Montilla Ibáñez. (ORL), Nicolas Fernandez Fernandez. (ORL), Jose Ignacio Abad Vivas-Pérez (urologia), Belén Gomez Navarro (OFT.), M. Teresa Belmonte García (DUE)).

Authors contribution

All authors contributed towards preparation of this manuscript.

Funding

This study was funded by the Consejería de Salud de la Junta de Andalucía, Spain. (Ref. PI-0410-2016).

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Correspondence to Gema Esteban Bueno.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Bueno, G.E., Ruiz-Castañeda, D., Martínez, J.R. et al. Natural history and clinical characteristics of 50 patients with Wolfram syndrome. Endocrine 61, 440–446 (2018). https://doi.org/10.1007/s12020-018-1608-2

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Keywords

  • Wolfram syndrome
  • Diabetes mellitus
  • Optic atrophy
  • Sensorineural deafness
  • Neurodegeneration
  • DIDMOAD