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Phenylalanine hydroxylase (PAH) deficiency (including phenylketonuria [PKU]) |
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Record Status This is a bibliographic record of a published health technology assessment. No evaluation of the quality of this assessment has been made for the HTA database. Citation Phenylalanine hydroxylase (PAH) deficiency (including phenylketonuria [PKU]) Lansdale: HAYES, Inc.. Genetic Testing Publication. 2013 Authors' conclusions Phenylalanine hydroxylase (PAH) deficiency, which has an estimated prevalence of 1 in 10,000 individuals, is a heritable disorder characterized by an inability to break down the essential amino acid phenylalanine (Phe). The PAH enzyme is encoded by the PAH gene, which is located on chromosome 12 at band q23.2. PAH is responsible for converting Phe to the amino acid tyrosine. An absence of adequate PAH enzyme activity leads to an accumulation of Phe in the blood, a condition known as hyperphenylalaninemia (HPA). A persistent excess of Phe in circulation negatively affects neurological development. PAH deficiency, which is caused by variants in the PAH gene, may be identified by measuring Phe and tyrosine levels in the blood and excluding other causes of HPA. It is typically classified based on Phe levels and daily Phe tolerance, when on an unrestricted diet. Individuals with a PAH deficiency may be diagnosed with classic phenylketonuria (PKU), moderate PKU, mild PKU, or mild HPA. Untreated, PKU is associated with intellectual disability, behavior problems, seizures, and other neurological dysfunction. In addition, pregnant
women with PKU are at risk of having a child with multiple congenital anomalies, as a result of the negative effects of excess Phe on embryonic development. Consequently, classic, moderate, and mild PKU require treatment in the form of a Phe-restricted diet and amino acid supplementation with a Phe-free formula. A subset of patients with a PAH deficiency—most frequently those with mild or moderate PKU and a higher level of residual PAH activity—experience a decrease in plasma Phe levels when treated with therapeutic doses of the PAH cofactor tetrahydrobiopterin (BH4). A BH4 response, which is determined by clinical testing, may allow for a less restrictive or even unrestricted diet. Those who are successfully treated (by diet and/or medication) and maintain a low level of Phe avoid the neurological consequences of PKU. The mildest form of PAH deficiency (i.e., mild HPA; also referred to as non-PKU HPA) is not associated with an increased risk of neurological problems and does not require treatment. Because PKU may be treated effectively, all 50 states in the United States (and many other countries) have adopted newborn screening for this disorder. As a result, affected individuals may be started on a Phe-restricted diet in the first days of
life, minimizing the chance of intellectual disability and other neurological dysfunction. Indexing Status Subject indexing assigned by CRD MeSH Phenylalanine; Phenylalanine Hydroxylase; Phenylketonuriass Language Published English Country of organisation United States English summary An English language summary is available. Address for correspondence HAYES, Inc., 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218 Email: hayesinfo@hayesinc.com AccessionNumber 32014000383 Date abstract record published 19/02/2014 |
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