, Volume 61, Issue 3, pp 440–446 | Cite as

Natural history and clinical characteristics of 50 patients with Wolfram syndrome

  • Gema Esteban BuenoEmail author
  • Dyanne Ruiz-Castañeda
  • Javier Ruiz Martínez
  • Manuel Romero Muñoz
  • Pedro Carrillo Alascio
Original Article



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


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.


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.


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.


Wolfram syndrome Diabetes mellitus Optic atrophy Sensorineural deafness Neurodegeneration DIDMOAD 



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.


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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

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


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Management Unit Garrucha, Area of Health Management North of AlmeríaSpanish Association for Research and Help to Wolfram SyndromeGarruchaSpain
  2. 2.Andalusian Public Foundation for the Biosanitary Research of Eastern Andalusia-Alejandro OteroSpanish Association for Research and Help to Wolfram SyndromeAndaluciaSpain
  3. 3.CIBERNEDDonostia University Hospital Neurology Service Area of Neurosciences Biodonostia Research InstituteSan SebastianSpain
  4. 4.Endocrinology and Nutrition UnitRafael Méndez HospitalGranadaSpain
  5. 5.Clinical Management Unit, Internal Medicine Hospital La InmaculadaArea of Health Management North of AlmeríaAlmeríaSpain

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