Maternal hyperphenylalaninemias in healthy Czech population of pregnant women: 30 years experience with screening prevention and treatment.

Introduction: The increased level of phenylalanine (Phe) in maternal blood - hyperphenylalaninemia (mHPA) has a detrimental effect on the early development of health foetus (1965). The toxic effect causes spontaneous abortion or retards intrauterine growth skeletal malformation cardiac anomalies can appear. However the most frequent are microcephaly mental retardation and hypotrophy. Patients and methods: Simultaneously with the introduction of obligatory "Newborn Screening Program" in CR also the facultative screening for mHPA was introduced ("Maternal Hyperphenylalaninemia Preventive Screening Program"). Since 1975 till now 222 990 healthy pregnant women (16-47 yrs) from city Prague and its area (cca 2 mil. inh. have been screened for increased Phe in bloody by Efrons chromatographic screening test (1964); Phe cut off value: 240 µmol/l. Nonfasting venous blood has been taken in 2nd-3rd month of pregnancy during the first antenatal visit. All positive cases have been verified with quantitative Phe estimation on amino acid analyzer incl. pterines analysis in urine. For differentiation on defected mHPAs the Gttlers scheme (1980) has been used. Mutations for Phe-hydroxylase gene analyzed by restriction enzyme digestion after Guldberg (1994). Results: The average incidence of mHPA detected at the beginning of pregnancy was found 1:8675. The major part (65.3%) of all detected mHPA belongs to mild or moderate form of phenylketonuria (PKU) with most frequent PAH gene mutations R408W Y414C IVS11 nt8g-a R158Q IVS12ntlg-a and R261Q. 19.2% corresponds to a typical or classical PKU with prevailing mutation R408W. Only in 15.3% were detected non- PKU (persistent HPA) with mutations R408W Y414C IVS12ntlg-a IV11nt8g-a and A403V. 28 offsprings born from pregnancies on low-phenylalanine diet (LPD) introduced at least 2 months before the conception and during the whole pregnancy show normal psychomotoric development. In 7 offsprings without LPD or after delayed introducing or on PLD or badlly monitored showed malformations (microcephaly hypotrophy skeletal malformations) od died. Discussion: Relatively high incidence of mHPA detected in healthy population of pregnant women of Prague area differs from findings of Buist (1989) or Levy (1994) from American pregnancy women screened for mHPA from umbilical blood. We consider that screening performed at the beginning of pregnancy from nonfasting venous blood is more effective compared to umbilical blood from two reasons: the Phe level in maternal blood is increased during first trimester of pregnancy due to succing effect of placenta in comparison to decreased Phe level at the end of labour. Umbilical blood for screening of mHPA is not quite suitable to detect the atypical or mild forms of Phe disturbances which prevailed in our Slavonic population of pregnant women. (authors)