The aim of this study is to unify the diagnostic and therapeutic standards in phenylketonuria. The course of the disease, diagnostic methods as well as treatment procedures is presented. Standards of treatment are based on the experiences and research carried out by the Screening Tests Unit of the Department of Public Health and the Clinical Department of Paediatrics of the National Research Institute of Mother and Child in Warsaw.

Mutations in the genes encoding different parts of phenylalanine hydroxylation system cause persistent hyperphenylalaninaemia. The most frequent form of hyperphenylalaninaemia is caused by mutations in the PAH gene. The most common variant result from defect of tetrahydrobiopterin synthase. Mutations in the PAH and PTS genes in the Polish population are presented. Genotype--phenotype correlations are discussed.

Background: 6-Pyruvoyl-tetrahydrobiopterin synthase (PTPS) is required for biosynthesis of tetrahydrobiopterin, the cofactor of various enzymes including the hepatic phenylalanine hydroxylase. Mutations in the PTS gene result in a variant type of hyperphenylalaninemia, requiring cofactor replacement therapy for treatment. Methods and Results: Four Polish patients with PTPS deficiency were screened for mutations in the PTS gene. Three novel mutations E35G, N36K, and F100V were identified. In one patient, a known mutation D136V was identified in both PTS alleles. Conclusions: Mutation D136V present in both alleles was proposed to be connected with a mild form of PTPS deficiency. The other three mutations were found in heterozygous patients with a central type of PTPS deficiency. D136V mutation is a common mutation in the Polish population.

Maternal phenylketonuria (M-PKU) is a syndrome of embryo- and fetopathy observed in the offsprings of mothers with increased blood level of phenylalanine. These women fall into two groups: phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP). The Phe--level safe for the fetus is 4-6 mg%. Typical for M-PKU syndrome is: microcephalia, mental retardation, intrauterine growth retardation, congenital heart diseases and other anomalies like esophageal atresia, meningocoele, Pierre-Robin syndrome, cataract. The only way to prevent this syndrome is Phe--restricted diet that should be initiated before conception. We reviewed updated literature on the pathogenesis of this syndrome, clinic, possibility of prophylaxis and treatment. We present also 5 pregnancies of 3 patients with PKU, treated in National Research Institute of Mother and Child in Warsaw. On that ground we propose the scheme of prevention of maternal PKU syndrome.

Early diagnosis and treatment of phenylketonuria (PKU) in Poland was started in 1965, initially on a voluntary and then on a obligatory basis.Guthrie tests have been used for newborn screening. For confirmation of diagnosis changing with time methods of blood phenylalanine (Phe) and tyrosine estimation were used. In addition, Phe and its urinary metabolites were estimated.A total of 560 cases of classical PKU, 99 mild hyperphenylalaninaemia and six atypical PKU cases were detected. The age of confirmatory estimations was from the 1st to 3rd month, in some cases above 3 months. Pretreatment Phe levels ranged from 12.5 to 70.7 mg/dl. The diet was started on a hospital basis and continued at home, controlled with Guthrie tests with age dependent frequency. Periodical multidimensional controls allowed evaluation of physical and mental development, together with biochemical scores (Hb, RBC, total plasma protein, Phe and tyrosin). In some patients trace elements (copper, iron, zinc and selenium) were also determined. Physical development of treated patients was normal. Biochemical scores presented transient relatively low Hb and iron concentrations especially in the youngest patients. DQ/IQ scores correlated with dietary control and social environment. In adults (age 19-26 years) off diet, mean IQ was 97.2 +/- 15.5 in those with good dietary control and 81.0 +/- 13.8 in those poorly controlled during treatment. In adults the average level of education attained was various types of professional school. Some patients attended or graduated from university.

The aim of present study was to evaluate the effectiveness of screening program for early detection of some metabolic errors in newborn population. The examinations included: early diagnostic of some amino acids and carbohydrates disturbances, cystic fibrosis and congenital hypothyreosis. Guthrie test and multidirectional urine screening test were used for the diagnostics of inborn errors in amino acids metabolism. Guthrie test for phenylalanine proved its high effectiveness and taking into account the relatively high frequency of phenylketonuria in our population this screening has been introduced as obligatory. The evaluation of pilot screening for tyrosinemia, homocystinuria and histidinemia in spite of no objections as to the tests themselves proved low frequency of these disorders in our country, sofar these tests have been abandoned. Multidirectional urine screening carried out in 6-8 weeks old infants allows for follow up control for some aminoacidopathies, and also for the detection of some transport metabolism and other metabolic errors. There is no doubt that screening tests for galactosemia should be carried out because of severe course of the disease and good results of its treatment. Problem to be discussed is the choice of screening procedure and age at which it should be performed. Cystic fibrosis being one of the most common disease in the group of metabolic disorders needs to be screened, because the detection allows for early introduction of complex palliative treatment. The comparative evaluation of three meconium tests for cystic fibrosis revealed dry paper meconium test to be the most useful and following to organize central screening center. Skin chloride system being fast and easy test is too expensive to be introduced as mass screening. Results of pilot screening study for congenital hypothyreosis point out the necessity for the mass diagnostic of this disorders. Choice of the test however is connected with economical aspects of the screening procedure.