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
Communication
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.
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. Other information about the project.