Percorrer por autor "Souza, Carolina"
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- Genotype/phenotype correlation in Glycogen Storage Disease type IXPublication . Rocha, Hugo; Lopes, Altina; Rodrigues, Esmeralda; Silva, Ermelinda; Trindade, Eunice; Vaio, Francisco; Souza, Carolina; Leão, Elisa; Vilarinho, LauraGlycogen Storage Diseases type IX (GSD IX) are caused by a deficient activity of glycogen phosphorylase kinase and are due to mutations in PHKA1, PHKA2, PHKB or PHKG2. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. It is a common form of glycogenosis and collectively, defects in these genes are responsible for 25% of all cases of GSD, occurring with a frequency of 1 100,000 live births, with the majority of patients presenting mutation in the X-linked PHKA2 (75% of the cases). Infants with GSD IX present with hepatomegaly, growth retardation and elevated transaminases. Ketotic hypoglycemia and hypotonia may also be present. It most of situations it is a mild GSD, with a benign course, with patients becoming asymptomatic as they grow up. Nevertheless, patients with mutations in the subunit γ (PHKG2) have been associated to more severe phenotypes including increased risk of liver cirrhosis or hepatocelular carcinoma. Our laboratory performs the molecular characterisation of Glycogen Storage Diseases type IX for seven years now (since 2008) and a total of thirteen patients were molecularly diagnosed. From these nine (eight males and one female) present mutation in the X-linked PHKA2, while the remaining three had mutations in PHKG2. Those with mutations in PHKG2 present severe phenotypes, resembling other hepatic GSD’s like GSD I and GSD III, in contrast to those with mutations in PHKA2. Our results allowed not only an easier confirmation of the clinical diagnosis, but also contribute to establish better follow up protocols according to the genotype.
- Molecular study is na importante tool in the confirmation of Inborn Errors of MetabolismPublication . Fonseca, Helena; Souza, Carolina; Vairo, Fillipo; Vilarinho, LauraThe urea cycle disorders (UCD) result from defects in the metabolism of waste nitrogen from the breakdown of protein and other nitrogen-containing molecules. Severe deficiency or total absence of activity of any of the first four enzymes (CPS1, OTC, ASS, ASL) in the urea cycle or the cofactor producer (NAGS) results in the accumulation of ammonia and other precursor metabolites during the first few days of life. Infants with a severe urea cycle disorder are normal at birth but rapidly develop cerebral edema and the related signs of lethargy, anorexia, hyper- or hypoventilation, hypothermia, seizures, neurologic posturing, and coma. Deficiencies in each of the enzymes result in specific UCD. Citrullinemia and argininosuccinic aciduria are autosomal recessive disorder that lead to the accumulation of nitrogen as ammonia, ala¬nine, glutamate, and other intermediate metabolites. The diagnoses of these disorders are based on clinical suspicion and biochemical and molecular genetic testing. Plasma and urine quantitative amino acid analysis, determination of plasma concentrations of ammonia and measurement of urinary orotic acid can distinguish between the specific urea cycle defects. A definitive diagnosis of a urea cycle defect depends on either molecular genetic testing or measurement of enzyme activity. The authors present a symptomatic Brazilian case that came to our lab with a diagnosis the citrullinemia. The amino acid profile obtained by HPLC show an increase of citruline in plasma. To clarify this case the genes ASS1 and ASL that encodes the enzyme argininosuccinate synthetase and argininosuccinate lyase were studied by reported methods. The molecular study of ASL has allowed the identification of the homozygous mutation in this patient: the splicing mutation c.524+2T>G. The mutation is described in the literature. In this case the molecular study was essential to the correct establishment of the diagnosis.
- MPV17: fatal hepatocerebral presentationPublication . Nogueira, Célia; Souza, Carolina; Husny, Antonette; Derks, Terry; Santorelli, Filippo; Vilarinho, Laura
- MPV17: fatal hepatocerebral presentation in a Brazilian infantPublication . Nogueira, Célia; Souza, Carolina; Husny, A.; Derks, Terry; Santorelli, Filippo; Vilarinho, Laura