RESUMO
Gamma-glutamylcysteine synthetase catalyzes the first step in glutathione synthesis. The enzyme consists of 2 subunits, heavy and light, with the heavy subunit serving as the catalytic subunit. A patient with hemolytic anemia and low red blood cell glutathione levels was found to have a deficiency of gamma-glutamylcysteine synthetase activity. Examination of cDNA from the patient and her mother showed that she was homozygous and that her mother was heterozygous for a A-->T transversion at nt1109 producing a deduced amino acid change of His370Leu. The partial genomic structure of the catalytic subunit of gamma-glutamylcysteine synthetase (GLCLC) was determined, providing some intron/exon boundaries to make it possible to sequence an affected part of the coding region from genomic DNA. The 1109A-->T mutation was not present in the DNA of 38 normal subjects. In the course of these studies we found a diallelic polymorphism in nt +206 of an intron and another polymorphism that consisted of a duplication of a CAGC at cDNA nt1972-1975 in the 3' untranslated region. The 2 polymorphisms were found to be only in partial linkage disequilibrium.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Substituição de Aminoácidos , Anemia Hemolítica/genética , Glutamato-Cisteína Ligase/genética , Deficiências da Aprendizagem/genética , Mutação Puntual , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Sequência de Aminoácidos , Anemia Hemolítica/sangue , Anemia Hemolítica/enzimologia , Animais , Sequência de Bases , Domínio Catalítico/genética , Códon/genética , Consanguinidade , Primers do DNA , DNA Complementar/genética , Eritrócitos/enzimologia , Feminino , Genes , Glutamato-Cisteína Ligase/deficiência , Glutationa/deficiência , Homozigoto , Humanos , Deficiências da Aprendizagem/sangue , Deficiências da Aprendizagem/enzimologia , Linfócitos/química , Camundongos , Dados de Sequência Molecular , Ratos , Proteínas Recombinantes de Fusão/metabolismo , Especificidade da Espécie , TransfecçãoRESUMO
PURPOSE: An acquired inhibitor to factor X is an uncommon clinical finding in the pediatric population. We report the development of this type of inhibitor in a pediatric patient with extensive burns. PATIENTS AND METHODS: The patient's clinical course was complicated by persistent blood loss from the burn site. RESULTS: Characterization of the inhibitor demonstrated that it bound to the light chain of factor X. CONCLUSIONS: The inhibitor disappeared after treatment with i.v. immunoglobulin.
Assuntos
Queimaduras/sangue , Fator X/antagonistas & inibidores , Antígenos/análise , Criança , Fator X/análise , Humanos , MasculinoRESUMO
Evaluation of hemolytic anemia in the newborn may be complicated owing to the physiologic changes that occur during this time; however, the newborn period is a time when congenital red cell abnormalities may first present and when maternal factors need to be considered. In this article, an approach to the diagnosis of hemolytic disease in the newborn is reviewed. The unique properties of the neonatal red cell, the normal red cell changes present in the neonate, the potential congenital defects and maternal factors that may influence the associated clinical and laboratory findings consistent with the diagnosis of hemolytic anemia, and a brief review of the red cell disorders associated with hemolytic anemia in the newborn are discussed.
Assuntos
Anemia Hemolítica , Anemia Neonatal , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/etiologia , Anemia Hemolítica/fisiopatologia , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/etiologia , Anemia Neonatal/diagnóstico , Anemia Neonatal/etiologia , Anemia Neonatal/fisiopatologia , Humanos , Recém-NascidoRESUMO
Cytogenetic analysis provides valuable prognostic information in children diagnosed with hematologic malignancies. While the t(4;11)(q21;q23) has frequently been reported in patients with acute lymphoblastic leukemia, the additional involvement of chromosome 13 to form a three-way translocation has not been described previously. We report a case of acute lymphoblastic leukemia in a 5-month old infant with a complex t(4;11;13)(q21;q23;q12-14).
