Zellweger syndrome

Zellweger syndrome
Zellweger syndrome
Classification and external resources
ICD-10 Q87.8
ICD-9 277.86, 759.8
OMIM 214100
DiseasesDB 14248
MeSH D015211

Zellweger syndrome, also called cerebrohepatorenal syndrome is a rare, congenital disorder, characterized by the reduction or absence of functional peroxisomes in the cells of an individual.[1] It is one of a family of disorders called leukodystrophies. Zellweger syndrome is named after Hans Zellweger, a former professor of Pediatrics and Genetics at the University of Iowa who researched this disorder.[2][3]

Contents

Molecular basis of disease

Zellweger syndrome is an autosomal recessive disorder caused by mutations in genes that encode peroxins, proteins required for the normal assembly of peroxisomes. Most commonly, patients have mutations in the PEX1, PEX2, PEX3, PEX5, PEX6, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26 genes.[4] In almost all cases, patients have mutations that inactivate or greatly reduce the activity of both the maternal and paternal copies of one these aforementioned PEX genes.

As a result of impaired peroxisome function, an individual's tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in peroxisomes. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed below. In addition, these individuals can show deficient levels of plasmalogens, ether-phospholipids that are especially important for brain and lung function.

Clinical manifestations of disease

Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD).[5] The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD).[6][7] Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.[8]

Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development.[5] In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions and, in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.[5]

Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts.[5] Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.[5][8]

Molecular diagnostics

In addition to genetic tests involving the sequencing of PEX genes,[9][10] biochemical tests have proven highly effective for the diagnosis of Zellweger syndrome and other peroxisomal disorders. Typically, Zellweger syndrome patients show elevated very long chain fatty acids in their blood plasma. Cultured primarily skin fibroblasts obtained from patients show elevated very long chain fatty acids, impaired very long chain fatty acid beta-oxidation, phytanic acid alpha-oxidation, pristanic acid alpha-oxidation, and plasmalogen biosynthesis.[5]

Prognosis

Currently, there is no cure for Zellweger syndrome, nor is there a standard course of treatment. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. Other treatment is symptomatic and supportive. Patients usually do not survive beyond one year of age.[5]

Additional resources for patients and families

  • European Leukodystrophy Foundation[11]
  • March of Dimes Foundation[12]
  • The Global Foundation for Peroxisomal Disorders[13]
  • United Leukodystrophy Foundation[14]
  • Zellwegers Support Network[15]

References

  1. ^ Brul S, W. A.; Westerveld, A.; Strijland, A.; Wanders, R.; Schram, A.; Heymans, H.; Schutgens, R.; Van Den Bosch, H. et al. (June 1988). "Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis" (Free full text). Journal of Clinical Investigation 81 (6): 1710–1715. doi:10.1172/JCI113510. PMC 442615. PMID 2454948. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442615.  edit
  2. ^ synd/1670 at Who Named It?
  3. ^ Wiedemann, H. R. (1991). "Hans-Ulrich Zellweger (1909-1990)". European journal of pediatrics 150 (7): 451–451. doi:10.1007/BF01958418. PMID 1915492.  edit
  4. ^ Online 'Mendelian Inheritance in Man' (OMIM) Zellweger syndrome; ZS -214100
  5. ^ a b c d e f g Steinberg, S.; Dodt, G.; Raymond, G.; Braverman, N.; Moser, A.; Moser, H. (2006). "Peroxisome biogenesis disorders". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1763 (12): 1733. doi:10.1016/j.bbamcr.2006.09.010.  edit
  6. ^ GeneReviews: Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum
  7. ^ Krause, C.; Rosewich, H.; Thanos, M.; Gärtner, J. (2006). "Identification of novel mutations inPEX2,PEX6,PEX10,PEX12, andPEX13in Zellweger spectrum patients". Human Mutation 27 (11): 1157. doi:10.1002/humu.9462.  edit
  8. ^ a b Raymond, G. V.; Watkins, P.; Steinberg, S.; Powers, J. (2009). Peroxisomal Disorders. pp. 631–670. doi:10.1007/978-0-387-30378-9_26.  edit
  9. ^ Steinberg, S.; Chen, L.; Wei, L.; Moser, A.; Moser, H.; Cutting, G.; Braverman, N. (2004). "The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum". Molecular Genetics and Metabolism 83 (3): 252–63. doi:10.1016/j.ymgme.2004.08.008. PMID 15542397.  edit
  10. ^ Yik, W. Y.; Steinberg, S. J.; Moser, A. B.; Moser, H. W.; Hacia, J. G. (2009). "Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders". Human Mutation 30: E467. doi:10.1002/humu.20932. PMID 19105186.  edit
  11. ^ http://www.ela-asso.com/?q=node/&lang=en&force=1
  12. ^ http://www.marchofdimes.com/
  13. ^ http://www.thegfpd.org/
  14. ^ http://www.ulf.org/
  15. ^ http://www.facebook.com/home.php?sk=group_125397297528689

External links

v · d · eCongenital abnormality · multiple abnormalities (Q87, 759.7)
Craniofacial
Short stature
1q21.1 deletion syndrome · Aarskog–Scott syndrome · Cockayne syndrome · Cornelia de Lange Syndrome · Dubowitz syndrome · Noonan syndrome · Robinow syndrome · Silver–Russell syndrome · Seckel syndrome · Smith-Lemli-Opitz syndrome-Turner syndrome
Limbs
Overgrowth
Laurence-Moon-Bardet-Biedl
Bardet–Biedl syndrome · Laurence-Moon syndrome
Combined/other,
known locus
v · d · eGenetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders (E80.3, 277.86)
Peroxisome biogenesis disorder
Zellweger syndrome · Autosomal adrenoleukodystrophy · Infantile Refsum disease · Adult Refsum disease-2 · RCP 1
Enzyme-related
Transporter-related
Lysosomal
See also: proteins, intermediates
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk

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Look at other dictionaries:

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  • Zellweger syndrome — A genetic disorder, also called the cerebrohepatorenal syndrome, characterized by the reduction or absence of peroxisomes (cell structures that rid the body of toxic substances) in the cells of the liver, kidneys, and brain. Zellweger syndrome is …   Medical dictionary

  • Zellweger syndrome — ▪ pathology        congenital disorder characterized by complete absence or reduction in the number of peroxisomes (peroxisome) in cells (cell). In the mid 1960s Swiss American pediatrician Hans Zellweger described the familial disorder among… …   Universalium

  • Zellweger syndrome — noun A rare congenital disorder characterized by the reduction or absence of peroxisomes in the cells of the liver, kidneys, and brain and the inability to beta oxidize very long chain fatty acids. Syn: cerebrohepatorenal syndrome …   Wiktionary

  • Zellweger — may refer to:* Zellweger off peak, the brand name of an electric switching device * Zellweger syndrome, a rare congenital disorderPeople with the surname Zellweger:* Marc Zellweger (born 1973), Swiss football defender * Renée Zellweger (born… …   Wikipedia

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