[Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience]. / Ocena przydatnosci badan przesiewowych u noworodków w swietle 35 lat doswiadczen wlasnych.

The results and the significance of neonatal mass-screening programmes for inborn errors of metabolism, conducted by the National Research Institute of Mother and Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the Beutler and Baluda test was introduced for galactosaemia, as well as the Efron urine test in infant screening for different inborn errors of metabolism. In the middle of the 70., neonatal mass-screening for cystic fibrosis (CF, mucoviscidosis) was started. Meconium tests and the sweat test with ion selective chloride electrode were used. Apart from inborn errors of metabolism, we also introduced a screening programme for neuroblastoma in which vaniline mandelic acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH level was assessed. The results of screening are shown in the tables and in the figures. In our opinion the best clinical results are obtained with screening for congenital hypothyroidism and for PKU, since very early detection and treatment in these diseases prevents severe mental retardation. We therefore consider that both these screening programmes should be treated as obligatory examinations in all neonates. Taking into consideration the fact that there are different types of hyperhenylalaninemias, the principles of differential diagnosis are discussed. Molecular genetic investigations, carried out in the NRIMC Department of Genetics proved to be a very important procedure in the verification of diagnosis of different mutations. The authors also discuss the problem of dietary treatment duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls, should not be discontinued during adolescence, since there is the problem of maternal PKU and the possibility of foetal damage. The results of our own investigations of maternal PKU are discussed. The significance of mass-screening for galactosemia is still under discussion. In our opinion, mass-screening for galactosemia is not useful and we have discontinued it. Selective screening has been started combined with molecular genetic studies in high risk families. In the future, we plan to prepare guidelines on the principles of diagnosis and treatment of galactosemia in children and women in the reproductive age. Mass-screening for cystic fibrosis is also still under discussion. The results of the early screening programmes were not satisfactory and the tests were discontinued. In 1998, after reorganisation of the whole system, CF screening, using tripsin-radioimmune assays, was started again. The new screening programme is combined with molecular genetic investigation of different mutations. It is still too early to assess the importance and success of this CF mass-screening programme. We decided to discontinue the screening for homocystinuria, histidinemia, tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not comply with criteria of mass-screening. In 1997, major reorganisation of screening programmes for inborn errors of metabolism, at NRIMC, was undertaken. The Guthrie test for PKU was changed to a quantitative colorimetric method. The immuno-luminometric method is used for TSH estimation. The whole system is based on complete computer control of all the steps of screening, from blood sampling on filter paper until the final diagnosis. The advantages of this modern system of organisation of the screening programme are discussed.

Hyperphenylalaninemia in Polish children's population.

Differential diagnosis in 144 cases of hyperphenylalaninemia detected through the newborn screening is discussed. In 123 infants phenylketonuria was diagnosed, so they were treated with the low phe diet. Verificatory examinations performed in diagnostically doubtful cases with the use of protein loading confirmed persistent enzymatic defect in all of them. In 21 infants with blood serum phenylalanine level below 15 mg% and lack of phe urinary metabolites, preliminary diagnosis of mild hyperphenylalaninemia was made and they were left without dietary treatment. A decrease with age in phenylalanine and tyrosine values was observed in this group. Mental development score, in the group as a whole, at age 3-7 years was normal. Two cases with relatively low IQ values have been discussed in regard to possible reason of their mental delay.

Early detection of inborn errors of metabolism in Poland.

A screening programme for early detection of inborn errors of metabolism in Polish newborn population has been evaluated. Guthrie bacterial inhibition assay for amino-acidopathies, Beutler and Baluda test for galactosemia, meconium test and ion-selective chloride electrode for cystic fibrosis, radioimmunological test for congenital hypothyroidism, and multidirectional urine screening test are described and the results discussed.

Experimental and clinical pharmacokinetics of nitrofurantoin in the early period of life.

The investigation of pharmacokinetics showed age-dependent rate of nitrofurantoin elimination in rats. Nitrofurantoin half-life of 0.41 hr in adults was prolonged to 0.95 hr in 2-weeks-old rats. Nitrofurantoin excretion rate was decreased in children younger than 2 years. Older children excreted in urine 44.32 +/- 16.07 and younger 25.07 +/- 5.7 per cent of the given dose of nitrofurantoin, indicating the lower capacity for nitrofurantoin elimination via kidneys.

[Progress in the early detection of inborn errors of metabolism]. / Postepy we wczesnym rozpoznawaniu genetycznie uwarunkowanych zaburzen metabolicznych.

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.

[Clinical and biochemical diagnosis of galactosemia among our cases]. / Kliniczna i biochemiczna diagnostyka galaktozemii na podstawie wlasnych przypadków.

Clinical and biochemical diagnostic studies concerned 17 cases of galactosemia coming from 15 not consauguineous families. Galactosemia was diagnosed between 1-st day and 11-th month of life. Tentative diagnosis based on clinical picture was made in 12 infants, others were detected through family history of galactosemia and/or biochemical newborn screening carried out at the National Research Institute of Mother and Child since 1969. Clinical symptoms of galactosemia occurred in most patients in the first week of life. They were the following (tab. II): hepatomegaly (in 94%), jaundice (81%), splenomegaly (79%), vomitus (62%) and diarrhoea in 56% of patients. Cataract was found in 6 infants (38%). Biochemical diagnosis was based on the results of enzymatic estimation of galactose-1-phosphate uridyl transferase activity in blood, galactose-1-phosphate in red blood cells and galactose in blood and urine. No activity of galactose-1-phosphate uridyl transferase was found in all patients, and the concentration of galactose-1-phosphate was higher than 25 mg/100 ml of red blood cells. High galactose level was observed in blood and urine in all patients with typical clinical course of galactosemia. In 2 patients however without clinical symptoms of the disease only trace amounts of galactose was detected in blood and urine. All these patients were treated with galactose free diet.

[Determination of the ribonuclease activity of the duodenal contents of children as a test in the differential diagnosis of cystic fibrosis and pancreatic exocrine insufficiency]. / Oznaczanie aktywnosci rybonukleazy w tresci dwunastniczej u dzieci jako test róznicujacy cystic fibrosis od niewydolnosci zewna trzwydzielniczej trzustki.

Ribonuclease activity was determined in the duodenal contents of healthy children, in children with cystic fibrosis and with pancreatic exocrine insufficiency. Assays were made at 7.0, in 0.05 M buffer without and with 0.35 M NaCl. The ratio of activity in 0.35 M NaCl to that in buffer alone was found to be 2.4 +/- 1.3 for children with cystic fibrosis as compared with 12 +/- 5 for the control group and children with pancreatic exocrine insufficiency.

[Binding capacity of some drugs to plasma proteins of newborns in comparison with adults (author's transl)]. / Bindungskapazität der Serumeiweisskörper von Neugeborenen und Erwachsenen für einige Arzneimittel.

Comparative studies on binding capacity of some drugs to plasma proteins of newborns and adults were carried out. Plasma from the newborn and adult rabbits as well as human from 4 sources: a) from healthy adults, b) from cord blood, c) from 5 days old newborns, and 6 month old infants were used for the experiments. For methodological reasons in the first part of our studies we have chosen: two sulfonamides - sulfamethazine and sulfamethoxasole, chlorpromazine and sodium salicylate. In the experiments two different techniques were used 1) equilibrium dialysis, 2) ultrafiltration. On the basis of the results obtained in animals as well as in human beings it was noted that the degree of drug binding to plasma proteins in newborns was different from that observed in adults, it may be higher or lower according to the drug used. The knowledge of this fact is of great importance, and should be taken into consideration in the calculation of proper dosage of various drugs in the newborns and infants.