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Molecular basis of D-bifunctional protein deficiency
G Möller1, E G van Grunsven, R J Wanders
1GSF-National Research Center of Environment and Health, Institute of Experimental Genetics, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany. gabriele.moeller@gsf.de
Insights
Peroxisomal disorders, affecting 1 in 5000 newborns, stem from enzyme deficiencies or assembly defects. This review details mutations in the D-bifunctional protein gene, causing severe Zellweger-like phenotypes.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Peroxisomal disorders occur in 1:5000 newborns, resulting from impaired peroxisomal functions.
- Phenotypes range from lethal in infancy (Zellweger syndrome) to mild disabilities (acatalasemia).
- Deficiency of D-bifunctional protein leads to a severe Zellweger-like phenotype.
Purpose of the Study:
- To review cases of D-bifunctional protein deficiency.
- To explore the molecular basis of these cases.
Main Methods:
- Review of reported human cases with D-bifunctional protein deficiency.
- Analysis of mutations in the gene encoding D-bifunctional protein.
Main Results:
- Identified various mutations in the D-bifunctional protein gene.
- These mutations cause partial or total loss of enzymatic function.
- Associated phenotypes are severe and Zellweger-like.
Conclusions:
- Mutations in the D-bifunctional protein gene are a significant cause of severe peroxisomal disorders.
- Understanding these molecular bases is crucial for diagnosis and potential therapies.
Abstract:
Peroxisomal disorders appear with a frequency of 1:5000 in newborns. They are caused either by peroxisomal assembly defects or by deficiencies of single peroxisomal enzymes. The phenotypes vary widely: affected humans may die very early in life within a few days to several months as a result of the impairment in essential peroxisomal functions as, for example, in Zellweger syndrome, or they may show only minor disabilities as is in acatalasemia. The deficiency of D-bifunctional protein, an enzyme involved in peroxisomal beta-oxidation of certain fatty acids and the synthesis of bile acids, causes a very severe, Zellweger-like phenotype. A number of different mutations in the gene coding for the enzyme were found in humans causing the total or partial loss of its enzymatic function. This paper gives a review of cases and their molecular basis.