Zellweger

Luther K and Troe J 1974 Photolytio oage effeot of iodine in gases at high pressure Chem. Phys. Lett. 24 85-90 Dutoit J C, Zellweger J M and van den Bergh H 1990 J. Chem. Phys. 93 242... 

Disorders affecting the import pathways to mitochondria, peroxisomes, and the nucleus (e.g., mutations in the peroxisomal Pex proteins leading to Zellweger syndrome). 

Fatal hereditary disorder that typically presents in the neonatal period. Clinical features include an array of hepatic, renal and neurological dysfunctions. Patients with Zellweger syndrome rarely survive the first year of life. The disease is caused by mutations in the Pex proteins leading to an defective import of peroxisomal matrix proteins and consequently to a loss of most peroxisomal metabolic pathways. 

MOST CASES OF ZELLWEGER SYNDROME ARE DUE TO MUTATIONS IN GENES INVOLVED IN THE BIOGENESIS OF PEROXISOMES... 

Interest in import of proteins into peroxisomes has been stimulated by studies on Zellweger syndrome. This condition is apparent at birth and is characterized by profound neurologic impairment, victims often dying within a year. The number of peroxisomes can vary from being almost normal to being virtually absent in some patients. Biochemical findings include an accumulation of very long chain fatty acids, abnormalities of... 

Zellweger, H. and Simpson, J. "Is Routine Prenatal Karyotyping Indicated in Pregnancies of Very Young Women "... 

Schaer BA, Zellweger MJ, Cron TA, Kaiser CA, Osswald S. Value of routine holler monitoring for the detection of paroxysmal atrial HhriUation in patients with cerebral ischemic events. Stroke 2004 35 e68-e70. 

Kennedy VC, Zellweger GW, Jones BF (1974) Filter pore-size effects on the analysis of Al, Fe, Mn, and Ti in water. Water Resource Res 10 785-790... 

IRD, infantile Refsum s disease NALD, neonatal adrenoleukodystrophy ZS, Zellweger s syndrome. 

Zellweger-spectrum-like Late onset neuropathy Refsum s disease... 

ALDP, DHAP, dihydroxyacetone phosphate DHAPAT, dihydroxyacetone phosphate acyltransferase NALD, neonatal adrenoleukodystrophy RCDP, rhizomelic chondrodysplasia punctata X-ALD, X-linked adrenoleukodystrophy ZS, Zellweger s syndrome. 

Table 41-4 shows that nine of the 12 Zellweger spectrum disorders show a considerable range of severity of clinical manifestations. Clinical and biochemical studies do not correlate with the type of gene defect. There is, however, considerable correlation between the severity of clinical manifestations and the degree to which a specific mutation compromises import function in vitro. For example in PEX1 deficiency, 75% of patients with the G843D allele, in which import is 15% retained, had the relatively mild IRD phenotype, compared to those with the C.2097insT, which abolishes import completely, where only 13% had the IRD phenotype. Such correlations also exist in patients with the PEX 7 defect [ 10]. 

Bifunctional protein deficiency. The enzyme defect involves the D-bifunctional protein. This enzyme contains two catalytic sites, one with enoyl-CoA hydratase activity, the other with 3-hydroxyacyl-CoA activity [13]. Defects may involve both catalytic sites or each separately. The severity of clinical manifestations varies from that of a very severe disorder that resembles Zellweger s syndrome clinically and pathologically, to somewhat milder forms. Table 41-6 shows that biochemical abnormalities involve straight chain, branched chain fatty acids and bile acids. Bifunctional deficiency is often misdiagnosed as Zellweger s syndrome. Approximately 15% of patients initially thought to have a PBD have D-bifunctional enzyme deficiency. Differential diagnosis is achieved by the biochemical studies listed in Table 41-7 and by mutation analysis. 

Barth, P. G., Majoie, C. B., Gootjes, J. et al. Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology 62 439-444, 2004. 

Bencala KE, McKnight DM, Zellweger GW (1990) Characterization of transport in an acidic and metal-rich mountain stream based on a lithium tracer injection and simulations of transient storage. Water Resour Res 26 989-1000... 

Uehlinger P, Zellweger M, Wagnieres G, Juillerat-Jeanneret L, van de Bergh H, Lange N... 

Enzyme defects are also known to exist in the minor pathways of fatty acid degradation. In Refsum disease, the methyl-branched phytanic acid (obtained from vegetable foods) cannot be degraded by a-oxidation. In Zellweger syndrome, a peroxisomal defect means that long-chain fatty acids cannot be degraded. 

Zellweger syndrome Is a llpid storage disorder caused by impaired peroxisome biogenesis due to deficiency or functional defect of one of eleven proteins involved in the complex mechanism of peroxisomal matrix protein import and assembly of the organelle. 

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