Peroxisomal disorders: clinical commentary and future prospects.
Recent progress in the classification, biochemistry, and molecular biology of peroxisomal disorders is reviewed from a clinical perspective. Diseases such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, hyperpipecolic acidemia, chondrodysplasia punctata, and Leber amaurosis share a common phenotype and involve deficiency of multiple peroxisomal enzymes. These disorders are associated with diverse metabolic abnormalities which are useful in pre- or postnatal diagnosis and distinguish these disorders from others such as X-linked adrenoleukodystrophy, adult Refsum disease, hyperoxaluria type I, and acatalasemia. Peroxisome structure is difficult to quantify histologically, since recent studies emphasize its developmental variability and tissue heterogeneity. The ability to manipulate this structure by dietary or pharmaceutical means provides a novel approach to therapy. At the molecular level, deficiency of peroxisomal enzymes responsible for fatty acid beta-oxidation or ether lipid synthesis reflects enhanced protein degradation due to abnormal peroxisomes; messenger RNA for the beta-oxidation enzymes is transcribed normally in peroxisomal disorders and can be increased by peroxisome proliferators. At least one integral structural protein of the peroxisome is synthesized normally in Zellweger syndrome. Hypotheses for the basic defect include defective regulation, uptake, or coenzyme stimulation of imported proteins, as well as defective biosynthesis. One clue to this defect may be a similar evolutionary history of peroxisomes and mitochondria which would explain their common alteration in Zellweger syndrome.
Wilson
G N
GN
Department of Pediatrics, William Beaumont Hospital, Royal Oak, Michigan.
Holmes
R D
RD
Hajra
A K
AK
D000326:Adrenoleukodystrophy / Q000235:genetics; D002675:Child, Preschool; D002806:Chondrodysplasia Punctata / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008830:Microbodies / Q000378:metabolism*; D015418:Optic Atrophies, Hereditary / Q000235:genetics; D010641:Phenotype; D012035:Refsum Disease / Q000235:genetics; D015211:Zellweger Syndrome / Q000235:genetics