[The hypercholesterolemias in pregnancy: their etiology and diagnostic significance considerations]. / Hypercholesterolémie v tehotenství: úvahy o jejich etiologii a diagnostickém významu.

OBJECTIVE: Analysis of gestational hypercholesterolemia incidence in Prague population of healthy pregnant women. Diagnostic significance of non-cholesterol sterols as suitable markers of endogenous synthesis and intestinal absorption in etiology of gestational hypercholesterolemia. DESIGN: Retrospective study. PATIENTS AND METHODS: From 21 000 healthy pregnant women set of 84 patients with blood level of total cholesterol >7.0 mmol/l where noncholesterol sterols had been analyzed by use of GC/MS method on Finnigan MAT 120b. Lathosterol and desmosterol as markers of endogenous syntesis and campesterol and sitosterol as markers for intestinal absorbtion. Classical lipid parameters have been analyzed on Beckman Coulter and Cobas analyzators. RESULTS: The median of total cholesterol values in the set of 21 000 healthy pregnant women - 6,8 mmol/l was observed; median of LDLCh - 4.6 mmol/l and HDLCh - 2.2 mmol/l. The frequency of hypercholesterolemia values > 8.0 mmol/l 1:132 (!) was observed. The average values were for lathosterol 7.8 ± 1.7 µmol/l; desmosterol 4.7 ± 0.9 µmol/l; campesterol 9.8 ± 2.6 µmol/l; sitosterol 9.6 ± 3.8 µmol/l. The correlations of lathosterol with total cholesterol r = 0.524 as well as with non-HDLCh r = 0.35 and LDLCh r = 0.36 were observed. In campesterol or sitosterol as well as HDLCh or TAG no significant correlations have been observed. DISCUSSION: Pilot study for gestational hypercholesterolemias in Czech population of healthy pregnant women proved the high frequency of increased levels of total cholesterol (> 8.0 mmol/l) 1:132. Increased levels of lathosterol values could explain the hypercholesterolemia in pregnancy as result of higher endogene synthesis of cholesterol. CONCLUSION: Relatively high frequency of hypercholesterolemia in pregnancy is caused according to our findings by increased endogenous synthesis of cholesterol via lathosterol. The highly increased values of cholesterolemia during pregnancy could be efectivelly used for detection and after ending of lactation period for further differential diagnostic and treatment of previously undiagnosed familial hypercholesterolemias.

Moderate hyperhomocysteinemia in patients treated for epilepsy.

Homocystein (Hcy) is regarded as a neuroexcitatory substance, which is therefore used as an epileptogenic agent in experimental epileptology. Experiments "in vivo" as well as "in vitro" revealed its relation to NMDA glutamate receptors, and its potential neurotoxicity. From the clinical aspect, hyperhomocysteinemia (HHcy), mostly as a marker of the risk factor in the vascular damage, was often studied in patients treated with antiepileptic drugs (AE). However, the neuroexcitatory influence of mild HHcy (up to 30 micromol/l) was rarely discussed. Out of a group of 123 adult patients on long-term conventional AE we analyzed 8 patients (7 men and one woman) with moderate to severe HHcy (30.7-109.0 micromol/l) retrospectively and 2-5 years after HHcy normalization. All of them suffered from partial and/or secondary generalized seizures accompanied by neuropsychological impairment depending on the aetiology of the disease. The patients were characterized by a concurrence of several factors: (1) All of them received conventional AEs inducing the cytochrome P 450 at the time HHcy was diagnosed. (2) Molecular-genetic tests showed enzymopathic impairment (methylentetrahydrofolate reductase-MTHFR mutation of the gene C677 T) also in all eight, homozygous in 7 cases and heterozygous in 1 case. (3) All patients were found to have a vitamin deficit or marginal values of at least one of the vitamins under study, especially folate and/or vitamin B6 and 812. With reference to clinical and EEG features, the potential neuroexcitatory influence of Hcy is discussed taking into account its effect on pathogenetic factors.

Genetic determinants of folate status in Central Bohemia.

Although several genetic factors have been implicated as determinants of blood folate concentration in various populations, their effect on folate status in the Czech population has not yet been examined. We explored whether blood folate concentrations in healthy Czech population are associated with polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR), folate hydrolase 1 (FOLH1), reduced folate carrier (RFC), and folate receptor (FOLR1) genes. In a cross-sectional study of 591 control subjects we determined genotypes by PCR-RFLP or ARMS-PCR methods, and plasma and erythrocyte folates by MEIA. The effect of different genotypes on folate status was examined by non-parametric tests and by regression analysis. The prevalence of the MTHFR 677C>T, MTHFR 1298A>C, FOLH1 1561C>T, RFC 80G>A and FOLR1 480G>C variant alleles was 0.34, 0.33, 0.05, 0.44 and 0.00, respectively. Only the MTHFR 677C>T variant was significantly associated with plasma folate concentrations (median 14.7, 14.0 and 12.2 nmol/l for the CC, CT and TT genotypes, respectively). Our study showed that among the five studied allelic variants, only the 677C>T polymorphism in the MTHFR gene is a significant genetic determinant of plasma folate concentrations in Czech population.

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 healthy 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 blood by Efron's chromatographic screening test (1964); Phe cut off value: 240 micromol/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 of detected mHPAs the Güttler's 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 atypical 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 badly monitored showed malformations (microcephaly, hypotrophy, skeletal malformations) or 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 pregnant 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. (Tab. 5, Fig. 7, Ref. 16.)

Complete proteinogram of cerebrospinal fluid and its contribution to the diagnostics of inflammatory and autoimmune diseases of the central nervous system.

Complete evaluation of cerebrospinal fluid proteinogram represents a routine request of the clinician in the analysis of CSF in the Czech Republic. It comprises the measurement of concentrations of acute phase proteins (CRP, orosomucoid, haptoglobin, transferrin, prealbumin), immunoglobulins (IgG, IgA, IgM), compressive markers (albumin, fibrinogen), markers of CNS tissue destruction (apolipoproteins A-I, A-II, Apo B), complement components (C3, C4), alpha-1-microglobulin, beta-2-microglobulin, and proteinase inhibitors (alpha-1-antitrypsin, antithrombin III). Therefore, 19 CSF proteins of precisely verified clinical relevance are routine parameters for the assessment of the functional state of the blood-CSF barrier, presence of the intrathecal synthesis of immunoglobulins, inflammatory changes and verification of CNS tissue destruction. Evidence of these clinically relevant and independent parameters enabled the detection of the presence of autoimmune and neuroinfective diseases of CNS, even in clinical cases where the basic CSF parameters do not express relevant changes, or they are of a bordering or non-specific character. Clinically typical and the most significant abnormalities in the CSF proteinogram represent themselves a new access to a contemporary CSF analysis. Despite the fact that assessment of CSF proteins and their analysis is quite a difficult field in laboratory medicine, it is now routinely requested and routinely performed in the Czech Republic.

[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.

[Homocysteinemia and ovariectomy--initial experience with functional monitoring]. / Homocysteinémie a ovarektomie--první zkusenosti s funkcním monitorováním.

OBJECTIVE: Metabolic study on plasmatic levels of homocysteine (Hcy) in 30 women post ovarectomy suffering from benign diseases. Based on previous pilot study by 6 women patients after ovarectomy the Hcy level increase has been supposed. Further objective was to detect possible change of homocysteinemia after application of estrogen replacement therapy (ERT). Hyperhomocysteinemia (HHC)--increased level of free amino acid homocysteine in blood--is considered on lipids independent risk factor in early development of cardiovascular diseases. The deficiency of 5,10-methylatetetrahydrofolate reductase (mutation C677T) is suspected as the main reason for decreased remethylation of Hcy. The group of women heterozygous for MTHFR mutation was compared with group of women patients without this mutation during the 8 weeks--monitoring after application of foliculostimulating hormone (FSH), estradiol (E2) for folate, vitamin B12 and Hcy in plasma. DESIGN: Basic study to get our own data about HHC in population of operated women before and after ovarectomy and after ERT. SETTING: Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University, Prague. METHODS: Total homocysteine in plasma was estimated by chromatographic method with use of fluorescence detection. The level of hormones in plasma was estimated by RIA test of DCL company. The mutation of gen for 5,10-MTHFR was estimated by genetic examination. Six blood taking were performed within 8 weeks. The 1st before ovarectomy, further 1., 3., 7., 28. and 56. day after operation. Since the 28th day 50 micrograms of 17-beta estradiol have been substituted by weekly transdermal system. RESULTS: No homozygote for 5,10-MTHFR has been found in the group of operated women, only 5 heterozygotes and 25 healthy homozygotes were found. Hcy values were similar in both groups. The patients were distributed into 2 groups according to their FSM level in the plasma (40 UI/I was stipulated as the limit). After ovarectomy the Hcy increased by both groups and after hormonal treatment the Hcy decreased. The folate level in both groups corresponded with Hcy level, in B12 vitamin concentration no dependence has been proved (P < 0.0001). CONCLUSION: Significant increase of Hcy levels after overactomy and subsequent decrease after substitutive treatment by estradiol. This correlation was followed by folate levels. No difference or correlation in monitored parameters was observed between heterozygotes for MTHFR and healthy homozygotes.

Subclinical course of cholesteryl ester storage disease in an adult with hypercholesterolemia, accelerated atherosclerosis, and liver cancer.

Few cases of asymptomatic cholesteryl ester storage disease (CESD) due to low enzymatic activity of human lysosomal acid lipase/cholesteryl ester hydrolase (hLAL) have been reported thus far in adults Here, we describe a 51-year-old man with a long clinical history of mixed hyperlipoproteinemia and severe premature atherosclerosis, but with no signs of hepatomegaly, liver dysfunction, or splenomegaly. The disease was discovered by chance in a biopsy performed because of suspected liver cancer (proven to be a cholangiocarcinoma). Residual hLAL activity in peripheral leukocytes was determined to be 6% of control values. DNA sequence and restriction fragment length polymorphism analysis demonstrated that the patient was a compound heterozygote for the prevalent CESD exon 8 splice site mutation (G934A) and the deletion of a C (nucleotide 673, 674, or 675) in exon 6 of the hLAL gene, resulting in premature termination of protein translation at residue 195. The patient died of liver failure as a consequence of extensive tumor infiltration at age 52. Lipid analysis revealed moderate cholesteryl ester storage in the liver and in the suprarenal cortex, and massive accumulation in the testicular histiocytes and Leydig cells, resulting in a pronounced secondary atrophy of the seminiferous tubules. Our case study demonstrates that hepatomegaly is an inconstant feature, even in CESD patients compound heterozygous for a Wolman mutation which results in complete loss of hLAL enzymic activity. It also highlights the need to be aware of this condition as it may be underdiagnosed.

[Homocysteinemia--its significance in gynecology and obstetrics]. / Homocysteinemie--její význam v gynekologii a porodnictví.

OBJECTIVE: Metabolic study on plasmatic levels of homocysteine (Hcy) in healthy women during normal or pathological pregnancy accompanied with corresponding levels of Hcy in amniotic fluid and foetal sera. Increased levels of Hcy--hyperhomocysteinaemia is respected as an independent risk factor accelerating the early development of vessel damage and causing the neural tube defects (NTD). DESIGN: Basic study to get our own data about Hcy in Czech healthy and population at risk of pregnant and non-pregnant women. SETTING: Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University, Prague. METHODS: Total homocysteine in plasma, amniotic fluid and foetal sera was estimated by chromatographic method with use of fluorescence detection. RESULTS: Normal homocysteine in preclimacteric healthy nonpregnant women is: 9.7 +/- 1.6 mumol/l with evident age-dependence. In healthy climacteric women are higher levels of Hcy (corresponding to the men values): 11.8 +/- 2.6 mumol/l. After use of hormonal contraceptives the plasmatic levels of Hcy decrease: 7.2 +/- 2.0 mumol/l. In physiological pregnancies Hcy reachs the lowest values: 4.4 +/- 1.7 mumol/l with any evident oscillations during pregnancy. In women in childbed period was Hcy 8.4 +/- 2.1 mumol/l observed. In pathological pregnanciesare its levels slightly elevated: 6.3 +/- 2.1 mumol/l, most evident in placental abruptions: 7.5 +/- 1.7 mumol/l. In pregnant women with susp. results of screening on M. Down only unsignificant increase of Hcy was observed: 6.12 +/- 2.4 mumol/l. In amnial fluids of healthy pregnant women are levels of Hcy are quite low: 4.1 +/- 1.2 mumol/l with any oscillations during pregnancy. In foetal sera of pregnancies at risk (NTD, susp., trisomy, inborn errors of metabolism): 3.6 +/- 1.4 mumol/l of Hcy was detected. The foetoplacental quotient for Hcy is 0.62. CONCLUSION: Average values for Hcy were established in physiological as well as in pathological pregnancies and till now only limited diagnostic significance has been observed. The hyperhomocysteinaemia mentioned in previous papers was not in NTD observed because our pregnant patients were regularly supplemented with all critical vitamins (folate, B6, B12).

[Clinical picture of homocystinuria with cystathionine beta-synthase deficiency in 19 Czech and Slovak patients]. / Klinický obraz homocystinurie z deficitu cystathionin beta-syntázy u devatenácti ceských a slovenských pacientu.

BACKGROUND: Homocystinuria due to cystathionine beta-synthase deficiency is an autosomal recessive disorder of methionine metabolism. It manifests with vascular, central nervous system and connective tissue disturbances, and phenotypically resembles Marfan's syndrome. We analysed the clinical course of homocystinuria in Czech and Slovak patients. METHODS AND RESULTS: The group of homocystinuric patients consisted of 19 individuals (12 males and 7 females) aged 5-32 years (average age 18 years), who were diagnosed between 1980 and 1999. The overall incidence of homocystinuria in the Czech and Slovak Republics was 1:287,000. The proportion of pyridoxine-responsive patients was 47%. The average follow-up period was 10 years (range 1 month to 19 years). The prevalence of the individual signs in the group was as follows: lens dislocation--95% of patients, progressive myopia--79%, marfanoid habitus--74%, kyfoscoliosis--68%, osteoporosis--63%, psychomotor retardation--58%, other neurologic symptomatology--58% and tromboembolism--21%. The average delay between the first sign of the disease and the time when the diagnosis was made was 4 years (range 1 to 14 years). At the time of diagnosis the average levels of metabolites in plasma were as follows: total homocysteine 348 mumol/l (range 211-536), free homocystine 70 mumol/l (range 0-203) and methionine 359 mumol/l (range 75-937). CONCLUSIONS: Both the clinical course of homocystinuria due to the cystathionine beta-synthase deficiency and its incidence in the Czech and Slovak Republics are similar to those in other populations. Since homocystinuria is a treatable disease, it should be included in the differential diagnosis of Marfan's syndrome, tromboembolism and severe psychomotor retardation.

[Diagnostic significance of mild hyperhomocysteinemia in a population of children with parents or grandparents who have peripheral or coronary artery disease]. / Diagnostický význam mírné hyperhomocysteinémie v populaci detí narozených z rodicu ci prarodicu trpících onemocnením periferních ci koronárních tepen.

BACKGROUND: A rise of the homocysteine plasma level--mild hyperhomocysteinaemia--is considered an independent risk factor for the development of vascular damage. It is due to hereditary deficiency of 5,10-methylene-tetrahydrofolate reductase with accentuation of vitamin deficiency (folic acid, vitamin B6 and B12). In previous studies the authors confirmed this fact in the population of patients with aortocoronary or peripheral arterial bypasses. The assumed autosomal recessive transmission of this deficiency should make it possible to detect carriers of this metabolic deviation already in childhood. By selective screening of the child population at risk it would thus be possible to detect affected subjects in time and prevent the development of vascular disease by preventive folate administration. METHODS AND RESULTS: In a group of 38 children and grandchildren from risk families where at least one of the parents or grandparents was operated on account of vascular obliterating disease the total homocysteine plasma level was examined by the chromatographic method. An increase of total homocystein (8.7 +/- 2.7 mumol/l) was found as compared with children from the non-risk population (5.4 +/- 1.8 mumol/l), (p < 0.001). The total homocysteine values however were dependent on the child's age and were more marked in children above 12 years of age. In the parental population mild hyperhomocysteinaemia was present in 38% of those with aortocoronary bypasses and in 43% of those with peripheral arterial bypasses. CONCLUSIONS: The authors found significantly elevated total homocysteine levels in the child population from risk families with obliterating vascular disease. The total homocysteine level depends on the child's age and is more markedly expressed in children above 12 years of age.

Statistical approaches for evaluation of genetic risk factor of peripheral arterial occlusive disease.

In the paper we show results of medical study from statistical point of view. The medical study was aimed to study genetic risk factors of peripheral arterial occlusive diseases in Czech population. Two genes, CBS and MTHFR were examined, as various genotypes of these genes are thought to have impact on amino thiols, who participate in variety of reactions in vasculature. Statistical part of the study was responsible for analysis and interpretation of collected data.

[Lysosomal acid lipase deficiency. Overview of Czech patients]. / Deficit kyselé (lysozomální) lipázy. Prehled ceských pacientu.

Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage of triacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediated LDL endocytosis are affected (liver, kidneys). There are two basic phenotypes. The fatal infantile phenotype (Wolman's disease) with generalized storage of both types of apolar lipids. This form was diagnosed in this country only once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterized by the storage of CE (which gave this entity the name of cholesteryl storage disease--CESD). Its main sign is affection of the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotic transformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increased VLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipids is a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases of CESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy with hepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patients with permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quite incidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis was established in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) and molecular genetic level (mutation in enzyme locus). In all instances mutation of G934A was found leading to reduction and loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations were heterozygous. In one instance for technical reasons only one allele was analyzed. In three instances a point "missense" mutation was found: T323A (Trp74Arg), T4(75)A (Asp124Glu), A210T (Asp36Gl), in one instance a "nonsense" mutation: C233T (Arg44-stop) and twice a deletion mutation delta C673-5 and delta G1068-8 leading to impairment of the reading frame and to premature stop of the codon.

Intellectual and school performance in adolescents with phenylketonuria according to their dietary compliance. The Czech-Slovak Collaborative Study.

The intellectual development and school performance of 81 adolescents with hyperphenylalaninaemia type I between the ages 15 and 19 years were evaluated in a retrospective study. All adolescents were born between 1975-1979. In spite of the continuous changes and improvement of dietary treatment, there were no differences in the dietary approach in all phenylketonuria centres involved. A significant negative correlation between IQ of adolescents with phenylketonuria and the onset of dietary treatment was observed (r = -0.37, P < 0.01). The best school performance was found in the group of adolescents with dietary therapy which was introduced in the first weeks of life. There was no correlation between IQ of the adolescents and their phenylalanine level in the neonatal period. There was a significant negative correlation between IQ of adolescents and the average level of blood phenylalanine in the first 5 years of life (r = -0.42, P < 0.01), but this correlation was less significant later on and was not present after the age of 14 years. Dietary compliance was much more difficult to achieve in adolescence than in childhood.

[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.

Analysis of growth curves of fowl. III. Geese.

1. Growth curves of two lines (S,D) and their reciprocal hybrids (in total,. n = 344) were evaluated by the Richards function. Geese were weighed at 7 d intervals to the ninth week, and then at 92, 154, 192 and 217 d of age. Food and water were supplied ad libitum. 2. The accuracy of curve fit measured by the coefficient of determination (R2) for different genetic groups ranged from 0.9840 to 0.9918. The highest percentage deviations between observed and estimated live weights were recorded at hatching (on average 15.1%), while at the others points of curve they were significantly lower (from 0.6 to 6.8%). 3. The geese are characterised by an early maturing rate. The peak of the absolute growth rate (the inflection point of the curve) occurred at 18.7 to 23.5 d of age (t+). The degree of maturity at a slaughter age of 63 d (u63 = y63/A) ranged from 0.69 to 0.76. Fitting the inflection point at the beginning of the linear growth phase significantly affects the maturing rate (k) and the ratio between the inflection (y+) and the asymptotic (A) weights. The values of these correlated parameters were very low (y+/A = 0.233 to 0.294, k = 0.0281 to 0.0373 ln theta/d). 4. The live weights of geese from 28 d of age and the parameters of the Richards function were significantly higher (P < 0.05, P < 0.01) in th sire line (S) than in the dam line (D). A low negative heterosis was observed at all points of the growth curves (-0.01 to -9.7%). The results indicated the effect of sex-linked growth genes. 5. The phenotypic correlations between parameters of the Richards function within genetic groups are discussed.