Zellweger disease
MIM.214100
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#