Maternal phenylketonuria

Phenylketonuria is the most common amino acid metabolism disorder. On average, phenylketonuria affects 1 in 8,000 people. The disease is based on a genetic disorder that leads to a sharp decrease or complete absence of the activity of the enzyme phenylalanine-4-hydroxylase, which converts phenylalanine to tyrosine. As a result of this metabolic block, toxic phenylalanine derivatives accumulate in the body, causing, among other things, a violation of lipid metabolism in the central nervous system. This mechanism is believed to be responsible for the progressive decline in intelligence in patients with phenylketonuria.

The main goal of the treatment of phenylketonuria is to reduce and regularly control phenylalanine in the patient’s blood. The best way to achieve this goal is to limit the amount of phenylalanine in the diet. It is recommended that all patients begin dietary therapy as soon as possible after diagnosis to prevent damage to the central nervous system. For all patients with phenylketonuria, lifelong diet therapy is recommended to prevent damage to the central nervous system and improve social adaptation.

Diet therapy for phenylketonuria is based on a sharp restriction of phenylalanine in the diet of patients due to the exclusion of high-protein foods and their replacement with specialized products partially or completely devoid of phenylalanine. In the diet of patients older than 1 year, as a rule, specialized amino acid mixtures without phenylalanine with a high protein content, enriched with vitamin and mineral complexes, are used.

Particular attention is paid to patients with phenylketonuria during preconception preparation and pregnancy to prevent the syndrome of maternal phenylketonuria.

Maternal phenylketonuria syndrome is an embryo fetopathy that develops in the fetus because of exposure to abnormal metabolic products of a pregnant woman with phenylketonuria in the absence of dietary treatment.

The following manifestations of maternal phenylketonuria syndrome are distinguished:

– Intrauterine growth retardation (IUGR). The frequency does not differ from the general population if the maternal phenylalanine level is controlled during the first 10 weeks of pregnancy and increases if the phenylalanine concentration is optimized later.

– Microcephaly. The risk is 5-18% during pregnancy, in which maternal phenylalanine levels are optimized prior to pregnancy and during the first 10 weeks. The risk increases to 67% if appropriate levels of phenylalanine are not reached within 30 weeks of pregnancy.

– Congenital heart disease and other malformations. Elevated maternal blood phenylalanine concentrations (> 600 µmol/L) during early pregnancy are associated with an approximately 8%-12% risk of heart malformations. Phenotypic features and other birth defects (including tracheoesophageal fistulas) have also been reported in children born to women with hyperphenylalaninemia.

– Intellectual deficiency (>90%). The critical value is maternal phenylalanine concentrations consistently above 360 ​​µmol/L during pregnancy, with an inverse relationship between the child’s cognitive function and maternal phenylalanine levels above 360 ​​µmol/L.

With constant treatment and monitoring of blood phenylalanine levels, the risk of congenital malformations of the fetus in a woman with hyperphenylalaninemia is minimal. Thus, strict adherence to a diet with a limited level of phenylalanine is the most important factor in the prevention of maternal phenylketonuria syndrome in the fetus.

In view of the ever-increasing number of children born to mothers with PKU, the development of public education programs for women with PKU during their childbearing years is critical. These programs should be tailored to the specific needs of patients, including early transition from pediatric to continuous adult care, and education of young partners with PKU.

Lifelong diet therapy is recommended for all patients with PKU to prevent damage to the central nervous system and improve social adaptation.

Medical genetic counseling is recommended for couples with a family history of children with HFA who are planning a pregnancy to inform about the possibility of prenatal diagnosis: prenatal diagnosis, the use of assisted reproductive technologies

Family planning counseling for adolescent girls and women with PKU is recommended to prevent the birth of a child with maternal phenylketonuria syndrome.

Information provided by the «Eurasian Council special nutrition product»