Zellweger Syndrome


Zellweger syndrome (Cerebrohepatorenal syndrome; Cerebro-hepato-renal syndrome) phenotype is caused by mutations in any of several different genes involved in peroxisome biogenesis, Peroxins (PEX proteins, peroxisomal transport proteins) proteins 1,2,3,5,6,12,14, and 26. Peroxin proteins serve several functions including the recognition of cytoplasmic proteins that contain peroxisomal targeting signals (PTS) that tag them for transport by peroxismnal proteins to the peroxisome. Zellweger syndrome is characterized by accumulation of cholesterol in plasma, tissues and cerebrospinal fluid, decreased chenodeoxycholic acid and increased concentration of bile alcohols and their glyconjugates. Increased concentrations of cholestanol and apolipoprotein B are also observed in spinal fluid.
Symptoms include dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, and seizures.

Pathway legend Zoom in

Pathway Image

Pathway legend Zoom in

References

  1. Uniprot: Q99424
  2. Uniprot: P22307
  3. OMIM: Entry 214100
  4. Aikawa J, Chen WW, Kelley RI, Tada K, Moser HW, Chen GL: Low-density particles (W-particles) containing catalase in Zellweger syndrome and normal fibroblasts. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10084-8. Pubmed
  5. Barth PG, Schutgens RB, Bakkeren JA, Dingemans KP, Heymans HS, Douwes AC, van der Klei-van Moorsel JM: A milder variant of Zellweger syndrome. Eur J Pediatr. 1985 Nov;144(4):338-42. Pubmed
  6. Brul S, Westerveld A, Strijland A, Wanders RJ, Schram AW, Heymans HS, Schutgens RB, van den Bosch H, Tager JM: Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis. J Clin Invest. 1988 Jun;81(6):1710-5. Pubmed
  7. Huybrechts SJ, Van Veldhoven PP, Hoffman I, Zeevaert R, de Vos R, Demaerel P, Brams M, Jaeken J, Fransen M, Cassiman D: Identification of a novel PEX14 mutation in Zellweger syndrome. J Med Genet. 2008 Jun;45(6):376-83. Epub 2008 Feb 19. Pubmed
  8. Muntau AC, Mayerhofer PU, Paton BC, Kammerer S, Roscher AA: Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am J Hum Genet. 2000 Oct;67(4):967-75. Epub 2000 Aug 24. Pubmed