RESUMO
Repeated evaluation of biotinidase (BTD) activity was carried out for a long-term follow-up in patients with hepatic glycogen storage diseases (GSDs). The results indicated inter-intra variability among the GSD-Ia, GSD-III and GSD-IX patients. In addition, a c.1330G>C transversion in the BTD gene, resulting in a p.Asp444His substitution was detected in one allele of a GSD-Ia patient with sustained normal enzyme activity. Thus far, it is necessary to be cautious in the interpretation of the results of BTD activity as a presumptive GSD diagnostic element. It is not known why plasma BTD activity increases in GSDs patients, or the clinical importance of the increment. When viewed from a global perspective, there are some lines of biotin biology that could indicate a relationship between BTD´s behavior and GSDs.
Assuntos
Biotinidase/sangue , Doença de Depósito de Glicogênio/enzimologia , Fígado/enzimologia , Argentina , Biomarcadores/sangue , Biotinidase/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Genótipo , Doença de Depósito de Glicogênio/sangue , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio Tipo I/enzimologia , Doença de Depósito de Glicogênio Tipo III/enzimologia , Humanos , Mutação , Fenótipo , Regulação para CimaAssuntos
Endopeptidases/biossíntese , Proteínas de Membrana/biossíntese , Lipofuscinoses Ceroides Neuronais/diagnóstico , Saliva/enzimologia , Adolescente , Adulto , Aminopeptidases , Argentina , Criança , Pré-Escolar , Dipeptidil Peptidases e Tripeptidil Peptidases , Saúde da Família , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Valores de Referência , Serina Proteases , Tioléster Hidrolases , Tripeptidil-Peptidase 1RESUMO
Glycogen storage disease type Ia (GSD-Ia) is caused by deleterious mutations in the glucose-6-phosphatase gene (G6PC). A molecular study of this gene was carried out in 11 Argentinean patients from 8 unrelated families. Four missense (p.Gln54Pro, p.Arg83Cys, p.Thr16Arg, and p.Tyr209Cys) and one deletion (c.79delC) mutations have been identified. Two novel mutations, p.Thr16Arg (c.47C>G) located within the amino-terminal domain and p.Tyr209Cys (c.626A>G) situated in the sixth transmembrane helix, were uncovered in this study. Site-directed mutagenesis and transient expression assays demonstrated that both p.Thr16Arg and p.Tyr209Cys mutations abolished enzymatic activity as well as reduced G6Pase stability.
Assuntos
Deleção de Genes , Expressão Gênica , Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/genética , Mutação de Sentido Incorreto/genética , Animais , Argentina , Western Blotting , Células COS , Cricetinae , Cricetulus , Análise Mutacional de DNA , Primers do DNA , Feminino , Glucose-6-Fosfatase/metabolismo , Doença de Depósito de Glicogênio Tipo I/metabolismo , Humanos , Masculino , Mutagênese Sítio-Dirigida , Monoéster Fosfórico Hidrolases/metabolismoRESUMO
We report the first case of isolated biotin resistant 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in Argentina. The diagnosis was established at 14 months of age by urinary organic-acid analysis and confirmed by enzyme assay in fibroblasts. The patient suffered from severe psychomotor retardation, hypotonia, areflexia, and failure to thrive, and died unexpectedly at 3 years 4 months of life. Brain MRI at 14 months showed signals of the white matter on cerebral T2-weighted, which were indicative of confluent and multiple foci of leukodystrophy, a pattern not previously described in this entity. In addition, high levels of oxypurines were detected in cerebrospinal fluid. This might be related to energetic consequences of the enzyme deficiency in the brain. This case extends the phenotype of isolated MCC deficiency in infancy and suggests this entity should be considered to be one of the possible causes of "metabolic leukodystrophies."