RESUMO
Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle proton pump. The ARCL-IIA syndrome characteristically presents a combined glycosylation defect affecting N-linked and O-linked glycosylations, differentiating it from other cutis laxa syndromes and classifying it as a Congenital Disorder of Glycosylation (ATP6V0A2-CDG). We studied two Mexican Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome. Both patients presented abnormal transferrin (N-linked) glycosylation but Patient 1 had a normal ApoCIII (O-linked) glycosylation profile. Mutational screening of ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported homozygous nonsense mutation c.187C>T (p.R63X) associated with a novel clinical finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X) mutation that had been previously reported but found that it also altered RNA processing generating a novel transcript not previously identified (r.2176_2293del; p.F726Sfs*10). This is the first report to describe Mestizo patients with molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their mutations are the first to be found in patients from different regions of the world and with different genetic backgrounds.
RESUMO
We describe clinical, biochemical, and molecular findings in a 2(1/2)-year-old girl with a phosphomannose isomerase deficiency who presented with severe and persistent hypoglycemia and subsequently developed protein-losing enteropathy, liver disease, and coagulopathy. Six months of therapy with mannose supplementation resulted in clinical improvement and partial correction of biochemical abnormalities.
Assuntos
Defeitos Congênitos da Glicosilação/diagnóstico , Hipoglicemia/etiologia , Pré-Escolar , Defeitos Congênitos da Glicosilação/dietoterapia , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/metabolismo , Suplementos Nutricionais , Feminino , Humanos , Hipoglicemia/metabolismo , Manose/uso terapêutico , Mutação Puntual , Análise de Sequência de DNARESUMO
Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface of polymorphonuclear neutrophils, and cell binding to E- and P-selectin was severely impaired, causing an immunodeficiency. The elevation of peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation of glycoconjugates bearing fucose in different glycosidic links was present in all cell types investigated, demonstrating that leukocyte adhesion deficiency II is not only a disorder of leukocytes but a generalized inherited metabolic disease affecting the metabolism of fucose.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Fucose/metabolismo , Síndrome da Aderência Leucocítica Deficitária/metabolismo , Proteína C-Reativa/análise , Cromatografia de Afinidade , Selectina E/metabolismo , Retardo do Crescimento Fetal/diagnóstico por imagem , Humanos , Lactente , Contagem de Leucócitos , Síndrome da Aderência Leucocítica Deficitária/sangue , Síndrome da Aderência Leucocítica Deficitária/diagnóstico por imagem , Antígenos CD15/análise , Masculino , Neutrófilos/imunologia , Selectina-P/metabolismo , Linhagem , Ultrassonografia Pré-NatalRESUMO
Genetic defects in glycoprotein metabolism usually result in neurologic symptoms, but newly discovered defects in glycoprotein biosynthesis (the carbohydrate-deficient glycoprotein syndromes) also present as severe gastrointestinal disorders with hypoglycemia, protein-losing enteropathy, and hepatic pathology. Glycosylation disorders may be more widespread than previously thought and can be detected by using a simple, but underutilized, serum test. Some patients may benefit from promising dietary therapies now in clinical trials.