title: D-bifunctional protein deficiency: a cause of neonatal onset seizures and hypotonia.
abstract: BACKGROUND
  Peroxisomal disorders are classified in two major groups: (1) peroxisome biogenesis disorders and (2) single peroxisomal enzyme/transporter deficiencies. D-bifunctional protein deficiency (OMIM #261515) is included in this last group of rare diseases and leads to an impaired peroxisomal beta-oxidation. D-bifunctional protein deficiencies are divided into four types based on the degree of activity of the 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase protein units.
  
  
  METHODS
  We present the first Portuguese reported type II D-bifunctional protein deficiency patient, whose neonatal clinical picture is indistinguishable from a Zellweger spectrum disease. The clinical features and the neuroimaging findings of polymicrogyria raised suspicion of the diagnosis. After biochemical analysis, D-bifunctional protein deficiency was confirmed with the identification of a homozygous p.Asn457Tyr (N457Y) mutation of the HSD17B4 gene. The patient's parents were carriers of the mutated allele, confirming the patient homozygosity status and allowing prenatal diagnosis in future pregnancies.
  
  
  CONCLUSIONS
  D-bifunctional protein deficiency is a rare, severe disease and the final diagnosis can only be accomplished after HSD17B4 gene sequencing. Treatment is supportive, aimed at improving nutrition and growth, controlling the central nervous system symptoms, and limiting the eventual progression of liver disease.
authors.affiliation: Department of Pediatrics, Centro Hospitalar do Porto, Porto, Portugal. Electronic address: nascimentojoao10744@gmail.com.
authors.forename: João
authors.initials: J
authors.lastname: Nascimento
authors.affiliation: Department of Neonatal Intensive Care Unit, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Céu
authors.initials: C
authors.lastname: Mota
authors.affiliation: Institute of Medical Genetics Jacinto Magalhães, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Lacerda
authors.affiliation: Institute of Medical Genetics Jacinto Magalhães, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Pacheco
authors.affiliation: Department of Neuropediatrics, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Chorão
authors.affiliation: Department of Pediatrics, Metabolic Diseases Unit, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Martins
authors.affiliation: Department of Neuropediatrics, Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Garrido
mesh_terms: D020739:Brain Diseases, Metabolic, Inborn / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology*; D004569:Electroencephalography; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009123:Muscle Hypotonia / Q000209:etiology*; D064029:Peroxisomal Multifunctional Protein-2 / Q000172:deficiency*; D012640:Seizures / Q000209:etiology*
chemical_list: D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human
keywords: D-bifunctional protein deficiency; neonatal seizures; peroxisome; polymicrogyria