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.
Subject(s)
Diabetes Mellitus/etiology , Optic Atrophy/etiology , Wolfram Syndrome/diagnosis , Adolescent , Adult , Child , Cross-Sectional Studies , Diabetes Insipidus/etiology , Disease Progression , Female , Hearing Loss, Sensorineural/etiology , Humans , Hypogonadism/etiology , Male , Middle Aged , Symptom Assessment , Wolfram Syndrome/complications , Young AdultABSTRACT
We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.
Subject(s)
Anemia, Megaloblastic/genetics , Databases, Genetic , Diabetes Mellitus/genetics , Hearing Loss, Sensorineural/genetics , Thiamine Deficiency/congenital , Wolfram Syndrome/genetics , Adolescent , Adult , Child , Child, Preschool , Exons , Family Health , Female , Genetic Association Studies , Genetic Variation , Genotype , Homozygote , Humans , Male , Phenotype , Prognosis , Sensitivity and Specificity , Thiamine Deficiency/genetics , Young AdultABSTRACT
En el año 2000, la Consejería de Salud de la Junta de Andalucía pone en marcha los procesos asistenciales integrados (PAI). El PAI correspondiente al embarazo, el parto y el puerperio, que implica tanto al médico de atención primaria como al obstetra, fue uno de los primeros en implantarse. Los avances en genética han propiciado una mejora en el diagnóstico precoz de anomalías genéticas, por ello es importante el conocimiento y la formación del médico de atención primaria en las técnicas de cribado. Objetivo: Valorar los conocimientos teóricos de los médicos de atención primaria sobre las técnicas de diagnóstico prenatal y si se consideran capacitados para ofrecer asesoramiento genético. Diseño: Estudio descriptivo transversal. Ámbito: Distritos sanitarios Valle del Guadalhorce (Málaga) y Condado-Campiña (Huelva). Población: Médicos de atención primaria de la zona que aceptaron participar, con exclusión de pediatras, médicos de urgencias y dispositivos de apoyo. Intervenciones: Mediante un cuestionario se evaluaron los conocimientos de los médicos de atención primaria y su percepción consciente en cuanto a su falta de conocimiento en el tema. Participaron 108 médicos, y se obtuvieron 100 cuestionarios válidos. Los datos se analizaron con el paquete estadístico SPSS 13.0 Windows. Conclusiones: Existe un alto índice de desconocimiento sobre las técnicas de diagnóstico prenatal por parte de los médico de atención primaria...
