Clinical and biochemical spectrum of D-bifunctional protein deficiency

Ann Neurol. 2006 Jan;59(1):92-104. doi: 10.1002/ana.20702.


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.

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency*
  • Blood Chemical Analysis
  • Bone and Bones / anatomy & histology
  • Bone and Bones / pathology
  • Brain / anatomy & histology
  • Brain / pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Enoyl-CoA Hydratase / deficiency*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Infant
  • Isomerases / deficiency*
  • Kidney / anatomy & histology
  • Kidney / pathology
  • Life Expectancy
  • Lipid Metabolism, Inborn Errors*
  • Liver / anatomy & histology
  • Liver / pathology
  • Magnetic Resonance Imaging
  • Multienzyme Complexes / deficiency*
  • Peroxisomal Bifunctional Enzyme
  • Peroxisomal Disorders* / classification
  • Peroxisomal Disorders* / pathology
  • Peroxisomal Disorders* / physiopathology
  • Surveys and Questionnaires


  • Multienzyme Complexes
  • 3-Hydroxyacyl CoA Dehydrogenases
  • EHHADH protein, human
  • Enoyl-CoA Hydratase
  • Peroxisomal Bifunctional Enzyme
  • Isomerases