[Anthropologic study of women with hyperphenylalaninemia]. / Antropologické vysetrení u zen s hyperfenylalaninémií.

OBJECTIVE: Anthropometric investigation in women with hyperphenylalaninemia. DESIGN: Retrospective clinical study. SETTING: Department of Obstetrics and Gynecology and Institute of Inherited Metabolic Disorders of General Faculty Hospital and 1st Medical Faculty of Charles University in Prague, Department of clinical Biochemistry, Hematology and Immunology of Hospital Na Homolce in Prague. METHODS: 44 anthropometric and 12 anthroposcopic parameters were studied in a group of 16 women with reproduction normality. RESULTS: Smaller body heights, pathological body posture and dysplastic findings were found. CONCLUSION: Registered differences and dysplastic findings are motivating for studies in a larger group of women with hyperphenylalaninemia.

[Sexual life of women with hyperphenylalaninemia]. / Vita sexualis zen s hyperfenylalaninémií.

OBJECTIVE: Characteristics of sexual life in women with hyperphenylalaninemia. DESIGN: Anamnestic study. SETTING: Department of Obstetrics and Gynaecology and Institute of Inherited Metabolic Disorders of General Faculty Hospital and 1st Medical Faculty of Charles University in Prague, Department of Clinical Biochemistry, Haemathology and Immunology of Hospital Na Homolce in Prague. METHODS: Characteristics of sexual life were studied in a group of 16 women with hyperphenylalaninemia. RESULTS: One fourth of the women lives without sex. In the rest of them sexual function is normal. CONCLUSION: One fourth of the women stays out of reproduction.

Mutation and haplotype analysis of phenylalanine hydroxylase alleles in classical PKU patients from the Czech Republic: identification of four novel mutations.

Mutations, haplotypes, and other polymorphic markers in the phenylalanine hydroxylase (PAH) gene were analysed in 133 unrelated Czech families with classical phenylketonuria (PKU). Almost 95% of all mutant alleles were identified, using a combination of PCR and restriction analysis, denaturing gradient gel electrophoresis (DGGE), and sequencing. A total of 30 different mutations, 16 various RFLP/VNTR haplotypes, and four polymorphisms were detected on 266 independent mutant chromosomes. The most common molecular defect observed in the Czech population was R408W (54.9%). Each of the other 29 mutations was present in no more than 5% of alleles and 13 mutations were found in only one PKU allele each (0.4%). Four novel mutations G239A, R270fsdel5bp, A342P, and IVS11nt-8g-->a were identified. In 14 (5.1%) alleles, linked to four different RFLP/VNTR haplotypes, the sequence alterations still remain unknown. Our results confirm that PKU is a heterogeneous disorder at the molecular level. Since there is evidence for the gene flow coming from northern, western, and southern parts of Europe into our Slavic population, it is clear that human migration has been the most important factor in the spread of PKU alleles in Europe.

[Is the anti-selection initiative in reproductive medicine anti-biological?]. / Je antiselekcní pocínání v reprodukcní medicíne antibiologické?

The human reproduction has the monotocial element of K strategy (nidifungous) with mature newborn mammals and also of the r strategy (nidiculous) with immature mammals. There are questions about "contra naturam" antiselective practice in the treatment of extremely premature newborns. Allometric equations were calculated form 93 species of mammals: Mneo = 0.03374 M0.946 and Gt = 68.536 M0.225 (Mneo is the body weight of newborns in kg, M is the body weight of the female in kg and Gt is the gestational period in days). According to these allometric equations the birthweight of newborns is from 1100 g to 1600 g and gestational age is from 22.4-24.5 weeks of gestation. The data from comparative zoology are in conformity with requirements of neonatologists to receive prematurity without further intra intrauterine pathologies. The postnatal care taken after extremely premature newborns replaces adaptive mechanisms which are present in immature mammalian newborns of r strategy. The neonatological practice has decreased the viability level to 24 weeks of gestation during the last 20 years. Further lowering to 22 weeks is possible in the near future.

[Mutation of the phenylalanine hydroxylase gene in the population of central Bohemia. Relation to the clinical picture of phenylketonuria]. / Mutace genu fenylalaninhydroxylázy ve stredoceské populaci. Vztah ke klinickému obrazu fenylketonurie.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive, disease, heterogeneous at the molecular level, caused by mutations in the gene of phenylalanine hydroxylase (PAH). The objective of the present work was to identify mutations and their frequency in the Central Bohemian and Prague population in relation to the clinical phenotype. METHODS AND RESULTS: The authors analyzed a group of 33 patients from 32 unrelated families. The phenotypic manifestations were classified as non-PKU hyperphenylalaninaemia (non-PKU-HPA), mild and classical PKU. Sixty-six mutant alleles of the PAH gene were analyzed by means of the polymerase chain reaction on a Perkin Elmer (480) apparatus and on PHC Techne. A total of eight mutations linked with five haplotypes were detected. R408W mutation linked with 2.4 haplotype was detected on 53% of mutant alleles. No type of mutation was detected by hitherto published procedures in 27% of mutant alleles. CONCLUSIONS: The finding on the distribution and frequency of mutations indicate a genotypic homogeneity of the PKU population in the Central Bohemian area and Prague and are consistent with hitherto published data from the Czech Republic. The revealed data can be used in prenatal and postnatal DNA diagnosis and genotype classification of PKU.

[Maternal hyperphenylalaninemia in a population of healty Czech women. 18 years' experience with mass screening, diet therapy and metabolic monitoring]. / Materské hyperfenylalaninémie v ceské populaci zdravých tehotných zen. 18leté zkusenosti s fakultativním screeningem, dietní lécbou a metabolickým sledováním.

BACKGROUND: Elevated phenylalanine levels in maternal blood (hyperphenylalaninaemia) during pregnancy damages the developing foetal tissues. Early detection of pregnant women with hyperphenylalaninaemia and adherence to a low phenylalanine diet already before conception and throughout pregnancy can prevent this damage. The objective of the investigation are results achieved screening and strict monitoring of low phenylalanine dietetic treatment in detected pregnant women of the Prague population. METHODS AND RESULTS: 186 350 healthy women of the Prague population were examined by the chromatographic screening test in a venous blood sample during their first visit in a maternity welfare centre and 22 positive cases were detected (incidence 1:8470). In 86% mild, persistent or benign forms of phenylketonuria were involved. Nineteen patients were treated by a low phenylalanine diet and the phenylalanine tolerance was monitored as well as the nitrogen balance, amino acids in serum and urine, protein markers, trace elements, vitamins, lipids, the body mass index-BMI, changes of body weight after introduction of the dietetic treatment and treatment during pregnancy. A significant increase of the phenylalanine tolerance by 20 to 200% was found, mostly in the second half of pregnancy and reduced values of serum and urinary selenium. The decrease of body weight when the diet was introduced and the increment during pregnancy correlated with the BMI value. In the other investigated parameters no significant deviations were found. CONCLUSION: Fifteen healthy children with normal psychomotor development delivered by 12 mothers with hyperphenylalaninaemia provide evidence of the effectiveness of prenatal screening for hyperphenylalaninaemia during pregnancy.