Manifestaciones clínicas y retraso diagnóstico en el síndrome de Wolfram

doi:10.1157/13090481

Revista Clínica Española

Volume 206, Issue 7, July 2006, Pages 332-335

https://doi.org/10.1157/13090481 Get rights and content

El síndrome de Wolfram (SW)

diabetes mellitus (DM), diabetes insípida (DI), ceguera y sordera, es multiorgánico, hereditario e infrecuente. Una disfunción mitocondrial altera los procesos oxidativos.

Objetivo

Analizar características clínicas, retraso diagnóstico de entidades constituyentes e impacto del diagnóstico precoz sobre morbimortalidad.

Material y métodos

Estudio descriptivo retrospectivo de 23 pacientes españoles con SW. Análisis de distintas entidades clínicas, edad de debut, tiempo transcurrido para el diagnóstico, causas de morbimortalidad, tratamiento administrado y consanguinidad entre progenitores.

Resultados

Prevalencia de componentes: DM y atrofia del nervio óptico (AO), el 100%; alteraciones audiológicas, el 95,65%; DI, el 82,6%; atrofia gonadal, el 75% de los varones; trastornos menstruales, el 87,5% de las mujeres. Otras entidades: alteraciones tracto urinario, neurológicas y cardíacas.

Conclusiones

La mayoría de los casos desarrollarán casi todas las complicaciones. La coexistencia de DM juvenil y AO es el mejor criterio diagnóstico. Un tratamiento precoz permitiría retrasar la progresión y controlar causas de mortalidad.

Wolfram’s syndrome (SW)

diabetes mellitus (DM), diabetes insipidus (DI), blindness and deafness, is multiorganic, hereditary and uncommon. Mitochondrial dysfunction damages the oxidative pathway.

Objective

To analyze the clinical characteristics, diagnostic delay in constituent diseases and early diagnostic impact over morbidity-mortality.

Material and methods

Descriptive retrospective study of 23 Spanish patients with SW. Different clinical entities analysis, onset age, lapse of time before diagnosis, morbidity-mortality causes, prescribed therapy and consanguinity between parents.

Results

Components prevalence: DM and optic atrophy (AO), 100%; auditory impairment, 95.65%; DI, 82.6%; gonadal atrophy, 75% in men; menstrual disorders, 87.5% in women. Other diseases: urinary tract, neurologic and heart disorders.

Conclusions

Most of the patients will develop almost all the complications. Juvenile DM in association with AO is its best diagnostic criteria. Early therapy should delay progression and control mortality causes.

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There are more references available in the full text version of this article.

Cited by (8)

Genetic protocol in primary care for rare diseases: Wolfram syndrome as a prototype
2022, Atencion Primaria
Las enfermedades raras, pese a su baja frecuencia individual, afectan globalmente al 7% de la población, por lo que el profesional de Atención Primaria (AP) tendrá varios de estos pacientes bajo seguimiento. El 80% de estas enfermedades tienen base genética, lo que hace fundamental un asesoramiento genético adecuado. El seguimiento de pacientes con síndrome de Wolfram (SW) puede servir para diseñar un protocolo susceptible de ser utilizado en el diagnóstico y manejo de otras entidades y ser utilizado por profesionales sanitarios para dar soporte a los pacientes, contando con la participación de profesionales sanitarios e investigadores especializados en el SW, los propios pacientes y su entorno. Se desarrollan los pasos fundamentales de todo procedimiento clínico genético, en el que la AP es clave para dar soporte a estas familias y transmitir de forma comprensible la información sobre los aspectos genéticos.
Rare diseases, despite their individual low frequency, affect 7% of the population all combined. Consequently, every primary care practitioner (PCP) will have several of these patients under his care. 80% of rare diseases are genetically determined, which makes genetic counseling fundamental in these cases. The follow-up of patients with Wolfram syndrome (WS) can be used to design a protocol to support these patients, with the participation of researchers and healthcare professionals specialized in WS, the patients themselves and their familial environment. This protocol can be suitable for the diagnosis and management of other diseases as well. The main steps of every genetic clinical procedure are developed in this article, emphasizing the role of PCP in supporting patients and their families and in transmitting genetic information in a comprehensible manner.
Wolfram syndrome. Clinical and genetic study in two families
2008, Anales de Pediatria
El síndrome de Wolfram, también conocido con la denominación DIDMOAD (por asociar diabetes insípida, diabetes mellitus [DM], atrofia óptica y sordera), es una causa muy poco frecuente de diabetes mellitus. Se encuentra dentro de los síndromes genéticos que pueden asociarse con diabetes en la clasificación de la American Diabetes Association (ADA). Es un cuadro neurodegenerativo con transmisión autosómica recesiva. Cursa con diversas manifestaciones clínicas, como la DM, la atrofia óptica, la diabetes insípida (DI), la sordera, la dilatación de las vías urinarias, alteraciones en el sistema nervioso central, alteraciones psiquiátricas y alteraciones gonadales; entre las más frecuentes destaca la DM, que es de aparición precoz y con poca prevalencia de cetoacidosis, y la atrofia óptica, la cual se considera el criterio diagnóstico fundamental en este síndrome. La DI suele aparecer más tarde. Este síndrome se presenta en la infancia, lo que da lugar a una mayor dificultad diagnóstica y terapéutica, con una elevada morbimortalidad y deterioro de la calidad de vida por las afectaciones neurológicas y urológicas. En el presente artículo describimos las características clínicas de 3 pacientes con síndrome de Wolfram y su evolución. En todos ellos existían antecedentes de consanguinidad. Se practicó análisis genético en los tres casos, uno presentó en homocigosis la mutación del gen WFS1 G736A en el exón 8, y los otros dos, que eran hermanos, homocigosis con la mutación del gen 425ins16 en el exón 4.
Wolfram syndrome (WS), also known as DIDMOAD (due to its association with diabetes insipidus, diabetes mellitus, optic atrophy and deafness), is an infrequent cause of diabetes mellitus. This syndrome is included among the genetic disorders associated with diabetes in the American Diabetes Association's classification. WS is an autosomal recessive neurodegenerative disease characterized by various clinical manifestations such as diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders and gonadal disorders. The most frequent of these disorders is early onset diabetes mellitus, with a low prevalence of ketoacidosis, and optic atrophy, which is considered a key diagnostic criterion in this syndrome. Diabetes insipidus usually develops later. This syndrome manifests in childhood, hampering diagnosis and treatment. Morbidity and mortality are high and quality of life is impaired due to neurological and urological complications. This article describes the clinical characteristics and outcome in three patients with WS. All three patients had antecedents of consanguinity. Genetic study was performed in all patients. One was homozygotic for the WFS1 gene that encodes the WFS1 G736A mutation in exon 8 and the remaining two patients, who were siblings, were homozygotic for the 425ins16 mutation in exon 4.
Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1
2024, Journal of Clinical Medicine
Sociobiomedical impact of overprotection: Wolfram syndrome as a paradigmatic example
2022, Cultura de los Cuidados
Natural history and clinical characteristics of 50 patients with Wolfram syndrome
2018, Endocrine
The quality of life in the relatives of Wolfram’s syndrome patients
2015, European Journal of Investigation in Health, Psychology and Education

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Notas clínicasManifestaciones clínicas y retraso diagnóstico en el síndrome de WolframClinical manifestations and diagnostic delay in Wolfram’s syndrome

El síndrome de Wolfram (SW)

Objetivo

Material y métodos

Resultados

Conclusiones

Wolfram’s syndrome (SW)

Objective

Material and methods

Results

Conclusions

Lancet

Int J Pediatr Otorhinolaryngol

Actas Urol Esp

Phenotype-genotype correlations in a series of wolfram syndrome families

Diabetes Care

Neurodegenerative disorders associated with diabetes mellitus

J Mol Med

Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product

Hum Mol Genet

WFS1/wolframin mutations, Wolfram syndrome, and associated diseases

Hum Mutat

Morbility and mortality in Wolfram syndrome

Diabetes Care

Juvenile DM, optic atrophy, hearing loss, diabetes insipidus, atonia of the urinary tract and bladder, and other abnormalities (Wolfram syndrome). Review of 88 cases from the literature with personal observations on 3 patients

Acta Pædiatr Scand Suppl

The syndrome of diabetes insipidus, DM, optic atrophy, deafness, and other abnormalities (DIDMOAD-syndrome). Two affected sibs and short review of literature (98 cases)

Klin Wochenschr

Notas clínicas
Manifestaciones clínicas y retraso diagnóstico en el síndrome de WolframClinical manifestations and diagnostic delay in Wolfram’s syndrome