Prevence poškození zdraví u hyperfenylalanémie - jedné z nejčastějších metabolických poruch

• Main Author: Havrlíková, Eva
• Other Authors: Pazdírková, Renáta
• Format: Dissertation
• Language: Czech
• Published: 2010
• Online Access: http://www.nusl.cz/ntk/nusl-284873

Phenylketonuria (PKU) is a metabolic disorder affecting the metabolism of essential aromatic amino acid phenylalanine. The mode of inheritance for PKU is autosomal recessive. Nearly all cases are caused by mutations in the gene encoding PAH and its deficiency, which has been mapped to chromosome 12. More than 500 have been identified, the most common mutation in The Czech Republic and in The Europe is R408W. The hepatic enzyme phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. Complete enzyme deficiency results in classical PKU, in which serum phenylalanine concentration exceeds 20 mg/dL (1200 micromol/L) and levels are elevated in the urine. Residual enzyme activity causes mild PKU (phenylalanine concentration 10 to 20 mg/dL, 600 to 1200 micromol/L) and mild hyperphenylalanemia (mild HPA, phenylalanine concentration 2.5 to 10 mg/dL, 150 to 600 micromol/L). Tyrosine concentration is normal or nearly normal. Tetrahydrobiopterin (BH4) is a cofactor required for PAH activity. Defects in BH4 metabolism account for approximately 1-2 percent of patients with elevated phenylalanine levels. In untreated patients, the hallmark of the disease is mental retardation and other neurological and psychical symptoms including epilepsy, but because of widespread neonatal screening,...