Clinical and biochemical spectrum of D-bifunctional protein deficiency.
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.
Ferdinandusse
Sacha
S
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
Denis
Simone
S
Mooyer
Petra A W
PA
Dekker
Conny
C
Duran
Marinus
M
Soorani-Lunsing
Roelineke J
RJ
Boltshauser
Eugen
E
Macaya
Alfons
A
Gärtner
Jutta
J
Majoie
Charles B L M
CB
Barth
Peter G
PG
Wanders
Ronald J A
RJ
Poll-The
Bwee Tien
BT
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
D009097:Multienzyme Complexes; D015094:3-Hydroxyacyl CoA Dehydrogenases; C576253:EHHADH protein, human; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases