Introduction
Phenylketonuria (PKU) is a hereditary disease with an autosomal recessive type of inheritance. Phenylketonuria is caused by insufficient activity of the enzyme called phenylalanine hydroxylase. As a result, it leads to the gradual accumulation of amino acid phenylalanine and its derivatives, which have a toxic effect on the central nervous system of a patient. Phenotypic manifestations of the disorder are microcephaly, convulsions, allergic dermatitis, hypopigmentation of hair, skin, and iris. Without timely treatment, patients with the problem have severe mental degeneration, and the seriousness of the PKU depends on the type of mutation.
In order to fully understand the hereditary nature of the disorder, it important to identify and describe the genes involved. The genes are autosomal recessive (AR), their location is 12q23.2, and the MIM number is 612349 in the locus PAH (“Phenylketonuria; PKU,” 2020). It is stated that transient phenylalanine titration treatment can have a detrimental effect on the control of the patients’ metabolism (Barbosa et al., 2018). Phenylketonuria is a genetic violation of the metabolism of amino acids and the reason is the lack of liver enzymes involved in the phenylalanine to tyrosine metabolism.
Main body
The early signs of phenylketonuria are vomiting, lethargy or hyperactivity, the smell of mold from urine and skin, and a delay in psychomotor development. Typical late symptoms include oligophrenia, physical developmental retardation, cramps, and eczematous skin changes. Screening of newborns for phenylketonuria is still in the maternity hospital. Subsequent diagnostics include molecular genetic testing, determination of blood phenylalanine concentration, urine biochemical analysis, and brain MRI. The treatment of phenylketonuria is to follow a special diet. Disruption of amino acid metabolism is accompanied by a violation of myelination of nerve fibers, a decrease in the formation of neurotransmitters, triggering pathogenetic mechanisms of mental retardation, and progressive dementia.
Newborns with phenylketonuria do not have clinical signs of the disease. Typically, the manifestation of phenylketonuria in children occurs at an early age. With the inception of feeding, the breast milk proteins or their substitutes begin to enter the baby’s body, which leads to the development of the early, non-specific symptoms such as lethargy, anxiety, and hyperexcitability, regurgitation, muscle dystonia, convulsive syndrome. One of the early pathognomonic signs of phenylketonuria is vomiting, which can be mistakenly treated as a manifestation of pyloric stenosis. By the following period, the child’s lag in the development of psychomotor functions becomes noticeable. The child can become inactive, irresponsive, stops to recognize parents, and does not attempt to stand on his feet or sit down. A fundamental factor in the treatment of phenylketonuria is a diet that restricts the intake of protein in the body.
Conclusion
Conducting a mass screening for phenylketonuria in the neonatal period allows organizing early diet therapy and prevent severe cerebral damage, impaired liver function. With the early appointment of an elimination diet in classical phenylketonuria, the prognosis for the development of children is good. With late treatment, the prognosis for mental development is poor. Prevention of complications of phenylketonuria consists of mass screening of newborns, early prescribing, and long-term dietary compliance. In order to assess the risk of giving birth to a child with phenylketonuria, preliminary genetic counseling should be given to couples who already have a sick child, are in a consanguineous relationship, and have relatives with this disease. Women with phenylketonuria who are planning a pregnancy should follow a strict diet.
References
Barbosa, C. S., Almeida, M. F., Sousa, C., Rocha, S., Guimas, A., Ribeiro, R., … Rocha, J. C. (2018). Metabolic control in patients with phenylketonuria pre- and post-sapropterin loading test. Journal of Inborn Errors of Metabolism and Screening, 6, 1-6.
Phenylketonuria; PKU. (2020). Web.