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What is PKU?
A basic, interactive explanation is found HERE

More detailed explanations The Medical Definition Symptoms Causes

The Genetics

The incidence of phenylketonuria in newborns is approximately one in ten thousand. It occurs in all ethnic groups, though it is more common in those having northern European ancestry.

The classical disease is due to a deficiency in the enzyme phenylalanine hydroxylase (PAH); the disease is transmitted as an autosomal recessive disorder. There are, however, other forms of the disease that are non-responsive to dietary therapy, and these forms are due to defects in enzymes related to the biosynthesis of the cofactor tetrahydrobiopterin, a required cofactor for the hydroxylation of phenylalanine and other aromatic amino acids.

Genetic analysis, using recombinant DNA techniques, has established that the genetic locus for PKU is on chromosome 12. The structural gene codes for a (mature) protein of 452 amino acids. SDS gel electrophoresis of purified enzyme shows two 50-kDa bands. The native enzyme is found in a polymeric form, but it is not clear if the subunits are identical or not.

<span style="font-family: Verdana,Geneva,sans-serif;">The PAH gene contains 13 exons of various sizes, spread over approximately 90 kilobases of DNA. DNA analysis has shown that the classical form <span style="font-family: Verdana,Geneva,sans-serif;">of the disease is due not to deletion of the entire gene for PAH, but is instead due to mutations within the gene's sequence leading to amino acid substitutions <span style="font-family: Verdana,Geneva,sans-serif;">or a premature stop codon. Numerous haplotypes at the PAH locus have been identified by restriction fragment length polymorphism analysis. <span style="font-family: Verdana,Geneva,sans-serif;">About three fourths of the patients of European ancestry with classical PKU are genetic compounds, with different mutations in each of their two copies of the PAH gene.


 * <span style="font-family: Verdana,Geneva,sans-serif;">Autosomal Recessive Genes **

<span style="font-family: Verdana,Geneva,sans-serif;">To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. <span style="font-family: Verdana,Geneva,sans-serif;">These disorders are usually passed on by two carriers. Their health is rarely affected, but they have <span style="font-family: Verdana,Geneva,sans-serif;">one mutated gene (recessive gene) and one normal gene (dominant gene) for the condition.

<span style="font-family: Verdana,Geneva,sans-serif;">Two carriers have a 25 percent chance of having an unaffected child with two normal genes (left), <span style="font-family: Verdana,Geneva,sans-serif;">a 50 percent chance of having an unaffected child who also is a carrier (middle), <span style="font-family: Verdana,Geneva,sans-serif;">and a 25 percent chance of having an affected child with two recessive genes (right).

<span style="font-family: Verdana,Geneva,sans-serif;">The Testing Process

<span style="font-family: Verdana,Geneva,sans-serif;">Living with PKU