Phenylketonuria (PKU) is one of the most common congenital metabolic diseases. It affects the metabolism of amino acid phenylalanine and follows autosomal recessive inheritance.
It can be distinguished between the more common classical phenylketonuria and the rare atypical phenylketonuria. In the classical phenylketonuria, there is a diminished or completely absent activity of the enzyme phenylalanine hydroxylase. This enzyme catalyzes the irreversible degradation of phenylalanine to tyrosine. As a result, phenylalanine accumulates. There is hyperphenylalanine, which particularly affects the development and function of the brain. Left untreated, the symptoms develop within the first four months after birth. These include psychomotor and mental developmental delays, muscular hypertension, hyperreflexia, and seizures. Eczematous skin lesions are frequently observed.
Patients often have light hair and blue eyes as a result of a lack of the pigment melanin. Through alternative metabolic pathways, phenylalanine is degraded to phenylpyruvic, phenylacetic and phenylmichloroacetic acids, especially the excretion of phenylacetic acid in urine and sweat, which causes a "case-like", musty odor of body and urine.
In the atypical phenylketonuria (about 2% of those affected by PKU) there is a defect in the coenzyme tetrahydrobiopterin (BH4). Without substitution of BH4, brain maturation is even more severely impaired than in the classical form, and children show neurological disorders as early as the neonatal period.
The disease is commonly diagnosed as part of neonatal screening. With an early onset treatment, a restriction of oral phenylalanine, the prognosis of classical phenylketonuria is extremely good. In case of atypical PKU, the prospects for untroubled development are not uniform.