ABSTRACT
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.
Subject(s)
Wolfram Syndrome/diagnosis , Wolfram Syndrome/genetics , Child , Child, Preschool , Female , Humans , MaleABSTRACT
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
