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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

  • failure to thrive

- craniofacial anomalies

  • large fontanelles
  • turribrachycephaly
  • flat occiput
  • macrocephaly
  • flat facies
  • round facies
  • micrognathia
  • high forehead
  • posteriorly rotated ears
  • sensorineural deafness
  • abnormal helices
  • upward slanting palpebral fissures
  • hypertelorism
  • epicanthal folds
  • brushfield spots
  • corneal clouding
  • cataracts
  • pigmentary retinopathy
  • pale optic disk
  • glaucoma
  • nystagmus
  • anteverted nares
  • high arched palate
  • protruding tongue
  • redundant skin folds of neck

- cardiovascular anomalies

  • ventricular septal defects
  • patent ductus arteriosus

- thoracic anomalies

  • pulmonary hypoplasia
  • bell-shaped thorax

- hepatic anomalies (hepatic Zellweger syndrome)

  • absent liver peroxisomes
  • intrahepatic biliary dysgenesis
  • prolonged neonatal jaundice

- digestive anomalies

  • pyloric hypertrophy

- genitourinary anomalies

  • cryptorchidism
  • hypospadias
  • external genitalia, female
  • clitoromegaly
  • hydronephrosis
  • renal cortical microcysts
  • absent renal peroxisomes

- skeletal anomalies

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

- limb anomalies

  • cubitus valgus
  • metatarsus adductus
  • transverse palmar crease
  • ulnar deviation of hands
  • talipes equinovarus
  • rocker-bottom feet
  • transverse palmar crease

- 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#