Phenylketonuria (PKU)– a congenital disease caused by a violation of the transition of phenylalanine to tyrosine and leading to mental retardation. Frequency. Significant ethnic and geographical differences in the frequency of different mutations in the most common classical PKU have been revealed. The frequency of classical PKU varies – 1:4,500 in Ireland, 1:8,000 in the white population of the USA, 1:12,000 in Italy, 1:16,000 in Switzerland, before a significant decrease in ethnic groups such as African Americans (1:50,000), Chinese and Japanese, Ashkenazi Jews. Unusually, PKU is not often observed in Finland (less often than 1:100,000); by 1995, 4 cases were identified. In Tatarstan, the frequency of the classic form of PKU is 1:6000 newborns (regardless of ethnicity). Genetic aspects – see Appendix 2. Hereditary diseases.

Clinical picture

    • Neurological and psychiatric disorders
    • Mental retardation
    • Increased excitability in childhood
    • Specific gait
    • Specific posture and sitting posture
    • Unconventional position of the limbs
    • stereotypical movements
    • Increased tendon reflexes
    • convulsions
    • Defective myelin formation
    • Microcephaly
    • Skin changes
    • Hypopigmentation
    • Dryness
    • Eczema
    • scleroderma
    • Hair is hypopigmented
    • Vomiting in the neonatal period
    • Light irises, cataract
    • Specific mouse body odor.

Research methods

    • X-ray studies: cerebral calcifications.
    • Laboratory research
    • Deficiency in phenylalanine hydroxylase (PKU-1), dihydropteridine reductase (PKU-2), or dihydrobiopterin synthetase (PKU-3)
    • Hyperphenylalaninemia
    • Phenylpyrovic acidemia
    • Increase in urine of o-hydroxyphenylacetic, phenylpyruvic and phenylacetic acids and phenylacetylglutamine.
    • Special Studies
    • The normal concentration of phenylalanine in the blood is 58+15 µmol/l in adults, 60+13 µmol/l in adolescents, and 62+18 µmol/l (average values ​​are indicated; + standard deviation) in babies. In newborns, the upper limit of normal is 120 µmol / l (2 mg / 100 ml)
    • With untreated classical PKU, the content of phenylalanine in the blood rises to 2.4 mmol / l.
    • Molecular Genetics: More than 200 different mutations of the phenylalanine hydroxylase gene are known. Most of them are linked to certain restriction fragment length (RFLP) and tandem repeat (VNTR) polymorphism haplotypes. The main mutation for the Slavic peoples is R408W/HP 2/VNTR 3. Note. A study conducted in Tatarstan showed a significant difference in the frequency of this mutation among patients with PKU of Russian (78%) and Tatar (37%) nationalities. Interestingly, among patients with PKU of Tatar nationality, often

(40%) noted mutations characteristic of the Mediterranean, incl. Turkic populations (R261Q, etc.), and no mutations characteristic of eastern peoples have been identified.


The regimen is outpatient, hospitalization is indicated to correct the diet in case of unstable concentration of plasma phenylalanine. A diet with a sharp restriction of the content of phenylalanine is introduced from the moment the diagnosis of classical PKU is confirmed. Given the high content of phenylalanine in the protein, animal products (meat, poultry, fish, mushrooms, milk and products from them) are completely excluded, the content of vegetable protein is carefully normalized, taking into account the body weight and age of the child. Deficiency of dietary protein and trace elements resulting from prolonged use of a restrictive diet is compensated by the appointment of special foods – mixtures of amino acids or protein hydrolysates with a low content of phenylalanine. Given the high cost of these products,

    • In atypical forms of phenylketonuria (2 and 3), even strict adherence to a diet low in plasma phenylalanine does not lead to the prevention of severe neurological disorders. The prescription of a diet enriched with tetrahydrobiopterin also does not lead to clinical improvement in such patients. Drug therapy
    • Drugs of choice
    • Nootropics such as piracetam
    • Acupuncture
    • To compensate for protein and vitamin deficiencies, when prescribing a restrictive diet, protein hydrolysis T and amino acid mixtures enriched with trace elements and vitamins are used: Lofenal k, Phenyl-100, Aphenylac (for babies up to a year old), PhenylFree, Tetrafen, Phenyl-400 (for babies after a year ). Dosages are calculated taking into account the content of natural protein in the diet, body weight and age of the child.
    • In atypical forms, the administration of dihydrobiopterin orally or intravenously can be effective. In treatment-resistant cases, some effect from the use of levodopa is noted.
    • precautionary measures. Trimethoprim, by blocking the synthesis of 7,8-dihydrobiopterin (a precursor of tetrahydrobiopterin, a cofactor of phenylalanine hydroxylase), may worsen the condition of patients with atypical PKU. Gene therapy. Of the 3 main steps required for gene therapy for phenylketonuria, 2 have been completed: cDNA has been obtained that provides the expression of human phenylalanine hydroxylase, and a hydroxylase-deficient animal model has been developed. However, vectors for efficient gene transfer in vivo require further development. Retroviral vectors, while quite efficient in vitro, have low transmission efficiency in vivo. Recombinant adenoviral vectors, although completely successful for a short time, do not persist in the body for more than a few weeks due to the immune response.

Current and forecast. Timely initiated dietary treatment avoids the development of clinical manifestations of classical phenylketonuria. It is necessary to carry out treatment before puberty, and according to individual indications, even longer. Because a woman with phenylketonuria cannot bear a healthy fetus, a special treatment is indicated, begun before conception and continuing until the moment of delivery, in order to exclude damage to the fetus by phenylalanine in the mother’s blood plasma. Pregnancy. An increased content of phenylalanine in the mother’s blood plasma leads to a variety of congenital diseases of the fetus, the spectrum depends on the severity and duration of the increase.

  • CHD at high concentrations of phenylalanine
  • Anomalies in the development of the brain, intrauterine and postpartum growth retardation, a wide bridge of the nose with everted nostrils with an average concentration of phenylalanine in the first trimester
  • Neurological symptoms with an average increase in the concentration of phenylalanine throughout pregnancy
  • Women with classic PKU are recommended a low-phenylalanine diet to achieve plasma phenylalanine concentrations.

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