Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.Phenylketonuria is a genetic disorder inherited from a persons parents. It is due to mutations in the PAH gene, which results in low levels of the enzyme phenylalanine hydroxylase. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is autosomal recessive, meaning that both copies of the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of a mutated gene typically do not have symptoms. Many countries have newborn screening programs for the disease.Treatment is with a diet that (1) is low in foods that contain phenylalanine, and which (2) includes special supplements. Babies should use a special formula with a small amount of breast milk. The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain a strict diet can have normal health and a normal life span. Effectiveness is monitored through periodic blood tests. The medication sapropterin dihydrochloride may be useful in some.Phenylketonuria affects about 1 in 12,000 babies.
In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed.Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. Hyperactivity, EEG abnormalities, and seizures, and severe learning disabilities are major clinical problems later in life. A characteristic "musty or mousy" odor on the skin, as well as a predisposition for eczema, persist throughout life in the absence of treatment.The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible including asthma, eczema, anemia, weight gain, renal insufficiency, osteoporosis, gastritis, esophagus, and kidney deficiencies, kidney stones, and hypertension). Additionally, major depressive disorders occur 230% higher than controls; dizziness and giddiness occur 180% higher; chronic ischemic heart disease, asthma, diabetes, and gastroenteritis occur 170% higher; and stress and adjustment disorders occur 160% higher. In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all. Genetics
PKU is an autosomal recessive metabolic genetic disorder.