Cirrosis en una lactante como manifestación de un defecto congénito de la glicosilación

Se presenta el caso de una recién nacida a término valorada en el servicio de urgencias por ictericia sin criterios de fototerapia. En los controles analíticos posteriores se detecta hipertransaminasemia y dislipemia con aumento de LDL-colesterol. Tras no objetivar alteraciones en los diferentes parámetros estudiados se realiza biopsia hepática que muestra hallazgos compatibles con cirrosis. Se amplía el estudio metabólico y presenta un perfil alterado de sialotransferrinas lo que lleva a realizar un diagnóstico de defecto congénito de la glicosilación. Bajo este nombre se incluye un grupo amplio de enfermedades relacionadas con alteraciones en el proceso de unión de glicanos a las cadenas proteicas. Este defecto, de origen genético, implica cambios en la estructura y funcionalidad de las glicoproteínas. Las manifestaciones clínicas son heterogéneas, en función del gen afecto y del tipo de glicoproteínas alteradas, siendo lo más común la afectación hepática, neurológica y hematológica. (provisto por Infomedic International)

We present the case of a full-term newborn girl evaluated in the emergency department for jaundice without phototherapy criteria. Subsequent laboratory tests showed hypertransaminasemia and dyslipidemia with increased LDL-cholesterol. After finding no alterations in the different parameters studied, a liver biopsy was performed showing findings compatible with cirrhosis. The metabolic study was extended and the patient presented an altered sialotransferrin profile, which led to a diagnosis of congenital defect of glycosylation. This name includes a broad group of diseases related to alterations in the process of glycan binding to protein chains. This defect, of genetic origin, involves changes in the structure and functionality of glycoproteins. The clinical manifestations are heterogeneous, depending on the gene affected and the type of glycoproteins altered, the most common being hepatic, neurological and hematological involvement. (provided by Infomedic International)

Hepatitis autoinmune y enfermedad celiaca en una paciente con hipertransaminasemia crónica

La hepatitis autoinmune es una patología poco frecuente en pediatría cuya incidencia ha aumentado en los últimos años. Aunque su espectro clínico es muy variado, debe sospecharse ante el aumento de transaminasas séricas tras haber descartado otras etiologías. A continuación, se presenta el caso de una paciente de 9 años con hipertransaminasemia crónica que fue diagnosticada de hepatitis autoinmune y enfermedad celiaca. (provisto por Infomedic International)

Autoimmune hepatitis is a rare pathology in pediatrics whose incidence has increased in recent years. Although its clinical spectrum is very varied, it should be suspected due to the increase in serum transaminases after having ruled out other etiologies. The case of a 9-year-old patient with chronic hypertransaminasemia who was diagnosed with autoimmune hepatitis and celiac disease is presented below. (provided by Infomedic International)

Biallelic variants in SLC35B2 cause a novel chondrodysplasia with hypomyelinating leukodystrophy.

Sulphated proteoglycans are essential in skeletal and brain development. Recently, pathogenic variants in genes encoding proteins involved in the proteoglycan biosynthesis have been identified in a range of chondrodysplasia associated with intellectual disability. Nevertheless, several patients remain with unidentified molecular basis. This study aimed to contribute to the deciphering of new molecular bases in patients with chondrodysplasia and neurodevelopmental disease. Exome sequencing was performed to identify pathogenic variants in patients presenting with chondrodysplasia and intellectual disability. The pathogenic effects of the potentially causative variants were analysed by functional studies. We identified homozygous variants (c.1218_1220del and c.1224_1225del) in SLC35B2 in two patients with pre- and postnatal growth retardation, scoliosis, severe motor and intellectual disabilities and hypomyelinating leukodystrophy. By functional analyses, we showed that the variants affect SLC35B2 mRNA expression and protein subcellular localization leading to a functional impairment of the protein. Consistent with those results, we detected proteoglycan sulphation impairment in SLC35B2 patient fibroblasts and serum. Our data support that SLC35B2 functional impairment causes a novel syndromic chondrodysplasia with hypomyelinating leukodystrophy, most likely through a proteoglycan sulphation defect. This is the first time that SLC35B2 variants are associated with bone and brain development in human.