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Molecular study is na importante tool in the confirmation of Inborn Errors of Metabolism
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Abstract(s)
The 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.
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Keywords
Genetica Metabolism Doenças Genéticas