Phenylketonuria PKU is an inherited disorder of metabolism that causes an increase in the blood of a chemical known as phenylalanine. Phenylalanine comes from a person's diet and is used by the body to make proteins. Phenylalanine is found in all food proteins and in some artificial sweeteners.
Without dietary treatment, phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious problems. Women who have high levels of phenylalanine during pregnancy are at high risk for having babies born with mental retardation, heart problems, small head size microcephaly and developmental delay.
This is because the babies are exposed to their mother's very high levels of phenylalanine before they are born. Newborn screening has been used to detect PKU since the 's.
As a result, the severe signs and symptoms of PKU are rarely seen. Symptoms of PKU range from mild to severe. Infants born with classic PKU appear normal for the first few months after birth.
However, without treatment with a low-phenylalanine diet, these infants will develop mental retardation and behavioral problems. Other common symptoms of untreated classic PKU include seizures, developmental delay, and autism. ArgGln showed BH 4 responsiveness. Even though p.
AlaThr has sufficient residual enzyme activity to ensure responsiveness. Although there was only one p. Ile65Thr is associated with near-normal levels of enzymatic activity and BH4 responsiveness. Of the 27 different mutations described herein, the p. Ile65Thr and p. AlaThr mutations were responsive to BH 4. These defects are located at opposite sides of the BH 4 -binding pocket. Specifically, the composite structural model of the PAH tetramer reveals that these mutations are in close proximity to the dimer interface and occur along the interface region of the regulatory domain.
This observation suggests that, upon mutation of p. Ile65Thr, p. AlaThr, and p. ArgCys, dimer stability is reduced. The increased BH 4 levels rescue dimer stability and, consequently, enzyme activity recovers to the normal level. In conclusion, exon deletions or duplication may be more frequent causes of PKU in Korean patients than in other ethnic groups.
Therefore, a gene dosage analysis should be considered as a complementary diagnostic tool for Korean PKU patients without point mutations in one or two chromosomes, and the long-range PCR method developed in the present study may be useful for screening Koreans for deletions of exons 5 and 6.
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Phenylketonuria mutations in Europe. Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Chang-Seok Ki. Reprints and Permissions. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common.
Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.
Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild cases may not require treatment with a low-phenylalanine diet.
Babies born to mothers who have PKU and uncontrolled phenylalanine levels women who no longer follow a low-phenylalanine diet have a significant risk of intellectual disability because they are exposed to very high levels of phenylalanine before birth.
These infants may also have a low birth weight and grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, an abnormally small head size microcephaly , and behavioral problems.
Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss. The occurrence of PKU varies among ethnic groups and geographic regions worldwide.
Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.
Mutations in the PAH gene cause phenylketonuria. The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase.
This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed effectively.
As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage. Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent.
People with untreated classic PKU have levels of phenylalanine high enough to cause severe brain damage and other serious health problems.
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