title: Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia.
abstract: D-bifunctional protein deficiency (#OMIM 261515) is a rare autosomal recessive hereditary metabolic disorder causing severe clinical and biochemical abnormalities that are usually fatal in the course of the first years of life. This disease is classified as single enzyme peroxisomal disorder affecting the β-oxidation pathway in this compartment. In this paper we present a full overview of the clinical presentation, magnetic resonance imaging, biochemical and molecular data of two Slovak D-bifunctional protein deficient patients. In the clinical presentation of both patients severe generalized hypotonia, depression of neonatal reflexes, craniofacial dysmorphism and seizures dominated starting from the second day of life. In both patients, who died up to two years of life, we found elevated plasma levels of very long chain fatty acids and we identified the presence of causative mutations in the HSD17B4 gene. In the first case, we found the homozygous mutation c.46G>A, which is responsible for a defect in the dehydrogenase domain. In the second patient, the heterozygous mutations c.1369A>G and c.1516C>T were present and functionally they are related to the hydratase domain of the protein. This combination of mutations in the second patient is very rare and has not been reported until now. The presence of mutations was examined in all family members, and the resulting data were successfully utilized for prenatal diagnosis.
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia. Electronic address: konkolovajanka@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Konkoľová
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: R
authors.initials: R
authors.lastname: Petrovič
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Chandoga
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Repiský
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: H
authors.initials: H
authors.lastname: Zelinková
authors.affiliation: M-Genetik, S.R.O., P. Mudroňa, 504/7, 03601 Martin, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Kršiaková
authors.affiliation: Department of Paediatric Neurology, University Pediatric Hospital, Comenius University, Faculty of Medicine, Limbova 1, 833 40 Bratislava, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Kolníková
authors.affiliation: Department of Medical Genetics, University Hospital F.D. Roosvelta, Námestie Ludvíka Svobodu 1, 975 17 Banská Bystrica, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Kantarská
authors.affiliation: 1st Department of Neurology, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: S
authors.initials: S
authors.lastname: Šutovský
authors.affiliation: Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Faculty of Medicine & University Hospital Bratislava, Mickiewiczova 13, 813 69 Bratislava, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Böhmer
mesh_terms: D001483:Base Sequence; D001928:Brain Diseases, Metabolic / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D064029:Peroxisomal Multifunctional Protein-2 / Q000172:deficiency* / Q000235:genetics; D020675:Peroxisomes / Q000201:enzymology; D018154:Slovakia
chemical_list: D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human
keywords: D-bifunctional protein deficiency; HSD17B4 gene; Peroxisomal β-oxidation of very long chain fatty acids