SVIBOR - Project code: 3-01-090


Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69


SVIBOR - Collecting Data on Projects in Croatia

Project code: 3-01-090

Inherited metabolic diseases in children

Main researcher: MARDEŠIĆ, DUŠKO (28220)

Type of research: applied
Duration from: 01/01/91. to 12/31/95.

Papers on project (total): 33
Papers on project quoted in Current Contents: 5
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Department of Pediatrics, University Hospital Centre Zagreb, Kišpatićeva 12, Rebro
Address: Kišpatićeva 12, Rebro
City: 10000 - Zagreb, Croatia
Phone: 385 (0)1 213 087
Fax: 385 (0)1 210 900

Summary: Research on phenylketonuria in Croatia. The object of this research project have been 82 children with hyperphenylalaninemia and their families discovered through the Croatian newborn screening program from 1979 to 1992 among 653844 blood samples screened. The incidence of all (classical, mild and benign) hyperphenylalaninemias in Croatia is about 1:8000 newborns, whereas the incidence of classical phenylketonuria (with 54 discovered children) is 1:12108 newborn infants. In 25 unrelated families from Croatia, using the Southern blot method with a 32P-labelled PAH cDNA probe and with allele-specific oliguncleotides the restriction fragment length polymorphism haplotypes (RFLP) at the phenylalanine hydroxylase locus have been studied. The result of RFLP analysis demonstrated that 80% of the mutant alleles were associated with only three haplotypes (1,2 and 4). Nine mutations were detected on the background of 7 mutant haplotypes, comprising 70% of PKU alleles in Croatia. The most frequent mutation was in codon 408, and the most frequent haplotype was haplotype 2 associated with this mutation. These data are in accordance with similar data from other European populations. The mutation on codon 281 has been found as being more frequent in the Croatian population as compared with any other population in Europe observed so far. The results of the study of other inherited metabolic diseases in Croatia are published in papers cited in the bibliography of this report.

Keywords: inherited metabolic diseases, genetics, mutations, phenylketonuria, hyperphenylalaninemias, haplotypes, PAH-gene, population genetics, Croatia

Research goals: The research under this project has two general aims: A. investigation of the epidemiology, clinical features and variability, and of the molecular genetics of classical phenylketonuria and other variants of hyperphenylalaninemia. B. Investigation of the clinical, biochemical and genetic features of other inherited metabolic diseases in children of Croatia. The investigational aims of the research quoted under A. can be summarized as follows: 1. Assessment of the incidence of phenylketonuria and other variants of hyperphenylalaninemia in the newborn population of Croatia in comparison with other European populations; 2. Assessment of the distribution of RFLP-haplotypes obtained by digestion of genomic DNA with appropriate restriction endonucleases; 3. Obtaining an insight into the molecular structure of the gene for phenylalanine-hydroxylase in the Croatian population; 4. Genotype-phenotype correlations of hyperphenylalaninemias The investigational aims quoted under B are: 1. Obtaining an insight into the epidemiology of the various inherited metabolic disease in Croatian children; 2. Assessment of the clinical and genetical peculiarities of these diseases in the Croatian population; 3. Evaluation of the therapetic possibilities and results for those diseases in our circumstances; 4. Creation of basic prerequisites for early diagnosis, long- term treatment and prevention and for genetic counceling in the population of Croatia.

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Last update: 10/11/95