title: Clinical and biochemical spectrum of D-bifunctional protein deficiency.
abstract: OBJECTIVE
  D-bifunctional protein deficiency is an autosomal recessive inborn error of peroxisomal fatty acid oxidation. Although case reports and small series of patients have been published, these do not give a complete and balanced picture of the clinical and biochemical spectrum associated with this disorder.
  
  
  METHODS
  To improve early recognition, diagnosis, prognosis, and management of this disorder and to provide markers for life expectancy, we performed extensive biochemical studies in a large cohort of D-bifunctional protein-deficient patients and sent out questionnaires about clinical signs and symptoms to the responsible physicians.
  
  
  RESULTS
  Virtually all children presented with neonatal hypotonia and seizures and died within the first 2 years of life without achieving any developmental milestones. However, within our cohort, 12 patients survived beyond the age of 2 years, and detailed information on 5 patients with prolonged survival (> or =7.5 years) is provided.
  
  
  CONCLUSIONS
  Biochemical analyses showed that there is a clear correlation between several biochemical parameters and survival of the patient, with C26:0 beta-oxidation activity in cultured skin fibroblasts being the best predictive marker for life expectancy. Remarkably, three patients were identified without biochemical abnormalities in plasma, stressing that D-bifunctional protein deficiency cannot be excluded when all peroxisomal parameters in plasma are normal.
authors.affiliation: Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, University of Amsterdam, Emma Children's Hospital, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. s.ferdinandusse@amc.uva.nl
authors.forename: Sacha
authors.initials: S
authors.lastname: Ferdinandusse
authors.forename: Simone
authors.initials: S
authors.lastname: Denis
authors.forename: Petra A W
authors.initials: PA
authors.lastname: Mooyer
authors.forename: Conny
authors.initials: C
authors.lastname: Dekker
authors.forename: Marinus
authors.initials: M
authors.lastname: Duran
authors.forename: Roelineke J
authors.initials: RJ
authors.lastname: Soorani-Lunsing
authors.forename: Eugen
authors.initials: E
authors.lastname: Boltshauser
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.forename: Charles B L M
authors.initials: CB
authors.lastname: Majoie
authors.forename: Peter G
authors.initials: PG
authors.lastname: Barth
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D001774:Blood Chemical Analysis; D001842:Bone and Bones / Q000033:anatomy & histology / Q000473:pathology; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004746:Enoyl-CoA Hydratase / Q000172:deficiency*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007223:Infant; D007535:Isomerases / Q000172:deficiency*; D007668:Kidney / Q000033:anatomy & histology / Q000473:pathology; D008017:Life Expectancy; D008052:Lipid Metabolism, Inborn Errors; D008099:Liver / Q000033:anatomy & histology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009097:Multienzyme Complexes / Q000172:deficiency*; D063994:Peroxisomal Bifunctional Enzyme; D018901:Peroxisomal Disorders / Q000145:classification / Q000473:pathology / Q000503:physiopathology; D011795:Surveys and Questionnaires
chemical_list: D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases