RESUMEN
Posttranslationally glycosylated proteins are important in many biological processes in humans and Congenital disorders of glycosylation (CDGs) are associated with a broad range of phenotypes. Type I CDGs are a group of rare autosomal recessive conditions. To date 17 subtypes have been enzymatically and molecularly characterized. Impaired function of the enzyme dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase encoded by the ALG8 gene, causes ALG8-CDG (CDG-Ih, OMIM #608104). This enzyme facilitates the transfer of a second glucose molecule to a growing lipid-linked oligosaccharide chain, a process that transpires in the endoplasmic reticulum (ER). We present a female patient of consanguineous parents, with pre- and postnatal growth retardation, dysmorphic features, significant developmental delay, visual impairment and an electrophoretic serum transferrin pattern indicative of a type I CDG. Type I CDG subgroup was determined by exome sequencing facilitated by homozygosity analysis. The patient was homozygous for two variants, nine nucleotides apart, in exon 8 of ALG8; c.799T > C [p.Ser267Pro] and c.808T > C [p.Phe270Leu]. Both missense mutations are predicted to affect a conserved region of an intraluminal ER loop of dolichyl pyrophosphate Glc(1)Man(9)GlcNAc(2) alpha-1,3-glucosyltransferase. To our knowledge, the current report describes the ninth published case of ALG8-CDG, contributing to the further delineation of this rare and variable disorder.
Asunto(s)
Errores Innatos del Metabolismo de los Carbohidratos/genética , Glucosiltransferasas/genética , Secuencia de Aminoácidos , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/mortalidad , Exoma/genética , Femenino , Glicosilación , Homocigoto , Humanos , Lactante , Datos de Secuencia Molecular , Mutación Missense , Análisis de Secuencia de ADNAsunto(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
A 13-year-old girl with previously undiagnosed fructose intolerance was operated on for acute appendicitis. Postoperatively she received several infusions containing fructose or sorbitol. Haematemesis occurred on the fourth postoperative day, as well as tarry stools and jaundice. Blood sugar was 2 mg/100 ml, Quick test 3%, liver enzymes were markedly elevated, serum bilirubin was over 9 mg/100 ml, and there was a metabolic acidosis. Despite intensive treatment, including haemodialysis and plasmapheresis, she died on the 11th postoperative day.