RESUMEN
We report a new patient with CDG Ig and review the five other known patients. From the data on this small number of patients, it seems that the association of psychomotor retardation, male hypogenitalism and decreased serum IgG in a patient with a type 1 pattern of serum sialotransferrins might be a clue to the diagnosis of CDG Ig.
Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/patología , Manosiltransferasas/deficiencia , Encéfalo/patología , Errores Innatos del Metabolismo de los Carbohidratos/sangre , Preescolar , Femenino , Homocigoto , Humanos , Inmunoglobulina G/sangre , Imagen por Resonancia Magnética , Masculino , Trastornos Psicomotores/diagnóstico , Sialoglicoproteínas/sangre , Transferrina/biosíntesis , Anomalías Urogenitales/diagnósticoAsunto(s)
Errores Innatos del Metabolismo de los Carbohidratos/genética , Glucosiltransferasas/deficiencia , Glucosiltransferasas/genética , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/enzimología , Errores Innatos del Metabolismo de los Carbohidratos/mortalidad , Análisis Mutacional de ADN/métodos , Femenino , Glicosilación , Humanos , Lactante , Recién Nacido , Masculino , Mutación/genética , Mutación/fisiología , Mutación Missense/genética , Mutación Missense/fisiología , Sitios de Empalme de ARN/genética , Sitios de Empalme de ARN/fisiologíaRESUMEN
Deficiencies in the pathway of N-glycan biosynthesis lead to severe multisystem diseases, known as congenital disorders of glycosylation (CDG). The clinical appearance of CDG is variable, and different types can be distinguished according to the gene that is altered. In this report, we describe the molecular basis of a novel type of the disease in three unrelated patients diagnosed with CDG-I. Serum transferrin was hypoglycosylated and patients' fibroblasts accumulated incomplete lipid-linked oligosaccharide precursors for N-linked protein glycosylation. Transfer of incomplete oligosaccharides to protein was detected. Sequence analysis of the Lec35/MPDU1 gene, known to be involved in the use of dolichylphosphomannose and dolichylphosphoglucose, revealed mutations in all three patients. Retroviral-based expression of the normal Lec35 cDNA in primary fibroblasts of patients restored normal lipid-linked oligosaccharide biosynthesis. We concluded that mutations in the Lec35/MPDU1 gene cause CDG. This novel type was termed CDG-If.