Zellweger syndrome; cerebrohepatorenal syndrome

Epidemiology: rare Genetics: - autosomal recessive disease - associated with defects in PEX2, PEX3, PEX5, PEX10, PEX12, PEX14, PEX16, PEX19, PEX26 genes - associated with defects in EHHADH expression - associated with defects in ABCD3 (type 2) Pathology: 1) absence of peroxisomes 2) decreased plasmalogens 3) increase in very long chain fatty acids (C-24 & C-26) 4) increase in cholestanoic acid derivatives (bile acid precursors) 5) abnormalities of the liver, kidney, brain & skeletal system 6) defective import mechanisms for peroxisomal matrix enzymes Clinical manifestations: 1) dysmorphic facial features a) cleft palate b) micrognathia 2) ocular abnormalities a) pigmentary retinopathy b) cataract 3) renal cysts 4) hearing impairment 5) psychomotor retardation (mental retardation) 6) severe hypotonia 7) areflexia 8) neonatal seizures 9) failure to thrive 10) hypertelorism 11) cubitus valgus 12) camptodactyly 13) metatarsus adductus 14) talipes equinovarus 15) cryptorchidism 16) apnea 17) jaundice 18) hepatomegaly Complications: in the severe form, death by age 12 months

Related

acetyl-Coenzyme A acyltransferase 1 (peroxisomal 3-ketoacyl CoA thiolase, peroxisomal 3-oxoacyl-Coenzyme A thiolase, beta-ketothiolase, thiolase-3, ACAA1, ACAA, PTHIO) ATP-binding cassette sub-family D member 3 (70 kD peroxisomal membrane protein, ABCD3, PMP70, PXMP1) dihydroxyacetone phosphate acyltransferase; DAP-AT; DHAP-AT; acyl-CoA:dihydroxyacetonephosphateacyltransferase; glycerone-phosphate O-acyltransferase (GNPAT, DAPAT, DHAPAT) lignocerate; lignoceric acid; tetracosanoic acid [C24:0] peroxisome peroxisome assembly factor 1; PAF-1; peroxin-2; peroxisomal membrane protein 3; 35 kD peroxisomal membrane protein; RING finger protein 72 (PXMP3, PAF1, PEX2, PMP3, PMP35, RNF72) phytanic acid phytanoyl-CoA dioxygenase, peroxisomal; phytanic acid oxidase; phytanoyl-CoA alpha-hydroxylase; phyH (PHYH, PAHX) plasmalogen

General

disease/disorder primarily affecting brain kidney disease; renal disease leukodystrophy lipid metabolism, inborn error; lipid storage disease; lipidosis liver disease peroxisomal biogenesis disorder

Properties

ACCUMULATION: CHOLESTANOIC-ACID lignocerate phytanic acid DEFICIENCY: peroxisome dihydroxyacetone phosphate acyltransferase phytanoyl-CoA dioxygenase, peroxisomal peroxisomal acyl-coenzyme A oxidase 3 acyl CoA dehydrogenase peroxisomal 3-ketoacyl CoA thiolase plasmalogen

Database Correlations

OMIM correlations MORBIDMAP 170993