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B Cabalska

Publications and source records attributed to B Cabalska.

At least 19 recordsLinked to original sources
PubMed2001

Should newborn mutation scanning for hyperphenylalaninaemia and galactosaemia be implemented? A Polish experience.

OBJECTIVE: To elucidate whether screening for mutations causing hyperphenylalaninaemia (HPA) and classic galactosaemia could provide important, additional information on a clinical phenotype. METHOD: Genotypes that cause disease at the phenylalanine hydroxylase (PAH) gene and galactose-1-phosphate uridyltransferase (GALT) gene in a group of 101 hyperphenylalaninaemic and 77 patients with classic galactosaemia were established. The PAH and GALT mutations were identified in genomic DNA extracted from whole blood leucocytes using single stranded conformational analysis and direct fluorescent sequencing of polymerase chain reaction (PCR) products. RESULTS: Mild HPA and mild phenylketonurea (PKU) were caused by divergent genotypes. In the studied group a total of 26 different mild and intermediate PAH mutations were identified, most of them being rare ones. Classic galactosaemia was caused by two frequent mutations, accounting for 82% of all mutated alleles. CONCLUSIONS: Identification of mild or intermediate mutations causing HPA could provide fast and reliable information about future clinical outcome of a newborn infant. Molecular diagnosis of HPA should be preceded by biochemical analysis and implemented to differentiate mild forms of HPA and cases of ambiguous classification. Because of multiple rare mutations scattered on all exons, scanning of the entire PAH coding sequence could be useful and cost beneficial. Routine genotyping is not proposed in classic phenylketonuria and classic galactosaemia, as it provides limited additional, prospective information on the clinical phenotype.

Adolescent↗
PubMed1999

Mutations in exon 3 of the PAH gene causing mild hyperphenylalaninemia.

Phenylketonuria (PKU), an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), is clinically very heterogeneous. On molecular level more than 350 mutations in the PAH gene are known to date, which in different genotype combinations could account for biochemical and clinical variability. Mutations located in exon 3 coding for a part of the regulatory domain of the PAH enzyme cause classical PKU, mild PKU, and mild hyperphenylalaninemia (MHP). We describe the phenotypic effects of seven mutations in exon 3 of the PAH gene (R68G, R68S, R71H, S87R, P89S, I95F, and A104D). We propose that mutations located between amino acid positions 71 through 94 cause MHP.

Adolescent↗
PubMed1998

Identification of Mutations Causing 6-Pyruvoyl- Tetrahydrobiopterin Synthase Deficiency in Polish Patients With Variant Hyperphenylalaninemia.

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.

Journal Article↗
PubMed1998

[Maternal PKU syndrome as an obstetric problem: literature review and own clinical experience].

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.

Adult↗
PubMed1997

Molecular basis of mild hyperphenylalaninaemia in Poland.

The major cause of the different forms of hyperphenylalaninaemia (HPA) is mutations in the gene encoding phenylalanine hydroxylase (PAH). The aim of this study was to determine the mutations responsible for mild forms of HPA and to relate different clinical phenotypes of HPA patients to their PAH genotypes. Four "mild" mutations, including the most frequent A403V and R297H mutations, occurred exclusively in mild hyperphenylalaninaemia (MHP). Mutations A104D, R243Q, R241H, and Y414C were detected in patients with mild phenylketonuria (mild PKU) only. These results may be useful in establishing a molecular differential diagnosis for PAH deficiency in Poland.

Humans↗
PubMed1994

Frequencies of the most common mutations responsible for phenylketonuria in Poland.

We screened 91 Polish phenylketonuric (PKU) children for the presence of 18 common mutations in the phenylalanine hydroxylase (PAH) gene, and 75.7% of PAH alleles were identified. The R408W mutation accounted for 54.9% of PAH mutant alleles. In the other 20.8%, eight mutations were detected: R158Q (6.6%), IVS10 (4.9%), IVS12 (2.7%), R261Q (2.2%), G272ter (1.65%), Y414C (1.1%), R252W (1.1%) and P281L (0.54%). Correlations between genotype and clinical phenotype were described.

Alleles↗
PubMed1990

[Evaluation of amino acids in plasma and amniotic fluid of women from genetic risk groups].

Plasma and amniotic fluid amino acids were assayed in 20 women of genetic risk groups in the second trimester of pregnancy. The age of patients ranged from 19 to 38 years. Indication for amnio-puncture were: chromosomal aberration or neural tube defect in previous pregnancy or age of pregnant women over 35 years. Blood and amniotic fluid were obtained with transabdominal amnio-puncture performed routinely in prenatal diagnosis. Amino acids were assayed with ion exchange column chromatography, using automatic amino acids analyzer LKB 4400. The obtained results were compared with plasma and amniotic fluid amino acids patterns in healthy women at the same trimester of pregnancy. The comparison of plasma aminograms revealed increased concentrations (above 100%) of cystine and alanine in the examined group. In women with neural tube defect in previous pregnancy and in those over 35 years of age, increased proline, leucine and valine (above 50%) concentrations were found. Decreased concentrations of glutamic acid (about 60%) was detected in women with chromosomal aberration in previous pregnancy and in those older than 35 years. Amniotic fluid amino acid pattern showed in all three patients groups decreased values arginine and ornitine (amino acids of the urea cycle), and also of cystine and taurine. In women with neural tube defect in previous pregnancy and in those older than 35, decreased concentration of lysine, serine and leucine was found. Also in the above 2 groups increasing tendency in comparison to the values in healthy women was observed for alanine (30-40%) and asparagine (150-215%). No correlation was observed between particular amino acids plasma concentration and amniotic fluid in our patients. Ratios of plasma to the amniotic fluid (P/FA) amino acid concentrations were calculated for the examined group and compared with those in healthy pregnant women. While in the last population most of the analyzed scores is below 1 which points higher amino acid concentration in amniotic fluid than that in plasma, performed analysis revealed; an increase in P/AF ratio by 214% in the group of "neural tube defect" women, alanine, glutamine and ornitine P/AF ratios were 35-50% than the normal value. P/AF ratio for cystine by 176%, for tyrosine--100% and for ornitine and arginine--55-65% respectively higher than normal in patients of "chromosomal aberration". P/AF ratio for glutamine acid was decreased by about 50%. In patients examined because of age above 35 years, P/AF ratio for cystine was increased by 200%, for alanine by 125%, for proline, histidine, ornitine, phenylalanine, I-leucine and metionine were increased by 30%-50%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Red blood cell glutathione peroxidase activity as a function of selenium supplementation in dietary treated children with phenylketonuria.

Red blood cell glutathione peroxidase (GSH-Px) activity of six patients with phenylketonuria treated with aminoacid mixture and protein hydrolysate diets was significantly lower (11.2 IU/g Hb) than that of 21 age-matched healthy children (14.9 IU/g Hb). When the diets were supplemented with yeast rich in selenium the red blood cell GSH-Px activity increased already after one month of treatment to 16.1 IU/g Hb (P less than 0.001) and remained at that level during subsequent two months of selenium supplementation. A high significantly positive correlation has been found between calculated red blood cell selenium level and GSH-Px activity within three months of selenium supplementation.

Child, Preschool↗
PubMed1985

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.

Diagnosis, Differential↗