Phenylketonuria

What is phenylketonuria?

Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the blood levels of a substance called phenylalanine. Phenylalanine is an amino acid (a building block of proteins) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, excess phenylalanine can build up to harmful levels in the body, causing mental retardation and other serious health problems.

The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment with a special low-phenylalanine diet, these children develop permanent mental retardation and behavioral problems. Seizures, delayed development, and movement disorders are also common. Affected 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 PKU (sometimes called moderate or mild PKU) have a smaller risk of brain damage. People with very mild cases may not require a special treatment diet.

Babies born to mothers with high levels of phenylalanine have a significant risk of mental retardation because they are exposed to very high levels of phenylalanine before birth. These infants may also grow more slowly than other children. Other characteristic medical problems include heart defects or other heart problems, small head size (microcephaly), and behavioral problems. Women with PKU and uncontrolled phenylalanine levels also have an increased risk of pregnancy loss.

How common is phenylketonuria?

Most cases of PKU are detected by newborn screening and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.

The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU is detected in 1 in 10,000 to 15,000 newborns.

What genes are related to phenylketonuria?

Mutations in the PAH gene cause phenylketonuria.

The PAH gene produces an enzyme called phenylalanine hydroxylase, which converts the amino acid phenylalanine to other essential compounds in the body. Normal levels of this amino acid are important for brain function. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet can build up to toxic levels in the bloodstream and other tissues. Excess phenylalanine damages nerve cells, resulting in brain damage.

Classic PKU, the most severe form of the disorder, occurs when phenylalanine hydroxylase activity is severely reduced or absent. As a result, people with untreated classic PKU have very high levels of phenylalanine that cause brain damage. Mutations in the PAH gene that allow some enzyme activity cause mild or moderate forms of PKU.

How do people inherit phenylketonuria?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Phenylketonuria on Wikipedia

'''Phenylketonuria''' (PKU) is a human genetic disorder that occurs in about 1 in 15,000 births, but the incidence varies widely in different human populations from 1 in 4,500 births among the Ireland to fewer than one in 100,000 births among the population of Finland.

History

Phenylketonuria was discovered by the Norwegian physician Ivar Asbjørn Følling, in 1934, when he noticed that hyperphenylalaninemia (HPA) was associated with mental retardation. In Norway this disorder is known as '''Følling's disease''', named after its discoverer. Dr. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease. His careful analysis of the urine of two retarded siblings led him to request many physicians near Oslo to test the urine of other retarded patients. This led to the discovery of the same substance that he had found in 8 other patients. The substance found had to be subjected to much more basic and rudimentary chemical analysis than is available today. He tested and found that reactions gave rise to benzaldehyde and benzoic acid, which led him to conclude the compound contained a benzene ring. Further testing showed the melting point to be the same as phenylpyruvic acid which indicated that that was the substance in the urine. His careful science inspired many to pursue similar meticulous and painstaking research with other disorders.

Genetics

PKU usually is caused by a defective gene for the enzyme phenylalanine hydroxylase (PAH). It is inherited as an autosomal recessive trait. A rarer form of the disease occurs when PAH is normal but its Cofactor (biochemistry) tetrahydrobiopterin (BH₄) is not synthesized by the patient. This enzyme normally converts the amino acid phenylalanine to tyrosine. If, due to a faulty or missing enzyme, this reaction does not take place, levels of phenylalanine in the body can be far higher ... [ Read More ]

External Resources

PKULife.com - Software designed to benefit those managing the PKU (Phenylketonuria) diet.

BioMarin Pharmaceutical Inc. - Researches and develops therapies for debilitating, fatal, chronic genetic disorders causing enzyme deficiency of carbohydrate metabolism, such as phenylketonuria. Headquarters in Novato, California. (Nasdaq: BMRN).

Medline Plus: Phenylketonuria - Definition, causes, symptoms and treatment.

Phenylketonuria - Definition, causes, symptoms and treatments.

Pediatric Oncall - In-depth look at Phenylketonuria (PKU). Includes symptoms, diagnosing, newborn screening, treatment and follow up.

Tuxes for Tia - A fund raising event for PKU research on behalf of the Piziali Family Foundation for PKU. Learn about phenylketonuria.

Genes and Diseases: Phenylketonuria - Brief genetic information.