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Zellweger disease

MIM.214100

Thursday 17 March 2005

Autosomal recessive Zellweger disease is a phenotype caused by mutations in any of several different genes involved in peroxisome biogenesis. Zellweger disease is the most severe of the peroxisome biogenesis disorders that are subdivided into 12 complementation groups (CGs).

Synopsis

- systemic anomalies

- craniofacial anomalies

- cardiovascular anomalies

- thoracic anomalies

- hepatic anomalies (hepatic Zellweger syndrome)

- digestive anomalies

  • pyloric hypertrophy

- genitourinary anomalies

- skeletal anomalies

  • stippled epiphyses (especially patellar and acetabular regions)
  • delayed bone age
  • wide cranial sutures

- limb anomalies

- cerebrospinal anomaies

  • severe mental retardation
  • hypotonia
  • hyporeflexia or areflexia
  • polymicrogyria
  • heterotopias/abnormal migration
  • subependymal germinolytic cyst (subependymal cysts) (7567228, 15170429)
  • agenesis/hypoplasic corpus collosum
  • hypoplastic olfactory lobes
  • small adrenal glands

Biology:

- Decreased dihydroxyacetone phosphate acyltransferase (DHAP-AT) activity
- Elevated long chain fatty acids
- Elevated serum iron and iron binding capacity
- Decreased plasmologen
- Increased phytanic acid
- Pipecolic acidemia
- Aminoaciduria
- Albuminuria

Etiology

Zellweger disease is a phenotype caused by mutations in any of several different genes involved in peroxisome biogenesis:

- peroxin-1 (PEX1) (MIM.602136) at 7q21
- peroxin-2 (PEX2) (MIM.170993) at 8q
- peroxin-3 (PEX3) (MIM.603164) at 6q
- peroxin-5 (PEX5) (MIM.600414) at Ch.12
- peroxin-6 (PEX6) (MIM.601498) at 6p
- peroxin-12 (PEX12) (MIM.601758)
- peroxin-14 (PEX14) (MIM.601791) at Ch.1
- peroxin-26 (PEX26) (MIM.608666)

Loci

- 1q22
- 1p36.2
- Chr.1
- 2p15
- 6q23-q24
- 7q11
- 7q21-q22
- 12p13.3
- 22q11.21

References

- Raafat F, Smith K, Halloran EA, Lacy D. Zellweger syndrome: a histochemical diagnosis of two cases. Pediatr Pathol. 1991 May-Jun;11(3):413-20. PMID: 1714076

- Applegarth DA, Dimmick JE. Adrenoleukodystrophy, cerebrohepatorenal syndrome (Zellweger syndrome), and peroxisomes. Pediatr Pathol. 1985;3(2-4):377-8. PMID: 4095031

- Powers JM, Moser HW, Moser AB, Upshur JK, Bradford BF, Pai SG, Kohn PH, Frias J, Tiffany C. Fetal cerebrohepatorenal (Zellweger) syndrome: dysmorphic, radiologic, biochemical, and pathologic findings in four affected fetuses. Hum Pathol. 1985 Jun;16(6):610-20. PMID: 3997138