Zellweger Syndrome: Difference between revisions
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Zellweger syndrome is the result of a mutation in any of the 12 PEX genes. Most cases of Zellweger syndrome are due to a mutation in the PEX1 gene. These genes control peroxisomes, which are needed for normal cell function. | Zellweger syndrome is the result of a mutation in any of the 12 PEX genes. Most cases of Zellweger syndrome are due to a mutation in the PEX1 gene. These genes control peroxisomes, which are needed for normal cell function. | ||
ZSDs are caused by mutations in one of the 13 different PEX genes. PEX genes encode proteins called peroxins and are involved in either peroxisome formation, peroxisomal protein import, or both. As a consequence, | ZSDs are caused by mutations in one of the 13 different PEX genes. PEX genes encode proteins called peroxins and are involved in either peroxisome formation, peroxisomal protein import, or both. As a consequence, mutations in PEX genes cause a deficiency of functional peroxisomes.<ref>Waterham HR, Ebberink MS. [https://www.sciencedirect.com/science/article/pii/S0925443912000932 Genetics and molecular basis of human peroxisome biogenesis disorders.] Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2012 Sep 1;1822(9):1430-41.</ref> Cells from ZSD patients either entirely lack functional peroxisomes, or cells can show a reduced number of functional peroxisomes or a mosaic pattern (i.e. a mixed population of cells with functional peroxisomes and cells without). Peroxisomes are involved in many anabolic and catabolic metabolic processes, like biosynthesis of ether phospholipids and bile acids, α- and β-oxidation of fatty acids and the detoxification of glyoxylate and reactive oxygen species. Dysfunctional peroxisomes therefore cause biochemical abnormalities in tissues, but also in readily available materials like plasma and urine. | ||
== Epidemiology == | == Epidemiology == | ||
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Introduction[edit | edit source]
Zellweger syndrome is a rare congenital disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual.[1] It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies. Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.
Zellweger spectrum disorder, also known as cerebrohepatorenal syndrome, is a rare inherited disorder characterized by the absence/reduction of functional peroxisomes in cells, which are essential for beta-oxidation of very long-chain fatty acids. It is autosomal recessive in inheritance, and the spectrum of the disease includes Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata type 1 (RCDP1) depending on the phenotype and severity.[2]
Etiology[edit | edit source]
Zellweger syndrome is the result of a mutation in any of the 12 PEX genes. Most cases of Zellweger syndrome are due to a mutation in the PEX1 gene. These genes control peroxisomes, which are needed for normal cell function.
ZSDs are caused by mutations in one of the 13 different PEX genes. PEX genes encode proteins called peroxins and are involved in either peroxisome formation, peroxisomal protein import, or both. As a consequence, mutations in PEX genes cause a deficiency of functional peroxisomes.[3] Cells from ZSD patients either entirely lack functional peroxisomes, or cells can show a reduced number of functional peroxisomes or a mosaic pattern (i.e. a mixed population of cells with functional peroxisomes and cells without). Peroxisomes are involved in many anabolic and catabolic metabolic processes, like biosynthesis of ether phospholipids and bile acids, α- and β-oxidation of fatty acids and the detoxification of glyoxylate and reactive oxygen species. Dysfunctional peroxisomes therefore cause biochemical abnormalities in tissues, but also in readily available materials like plasma and urine.
Epidemiology[edit | edit source]
The incidence of ZSDs is estimated to be 1 in 50.000 newborns in the United States.[4] It is presumed that ZSDs occur worldwide, but the incidence may differ between regions. For example, the incidence of (classic) Zellweger syndrome in the French-Canadian region of Quebec was estimated to be 1 in 12 [18]. A much lower incidence is reported in Japan, with an estimated incidence of 1 in 500.000 births [19]. More accurate incidence data about ZSDs will become available in the near future, since newborn screening for X-linked adrenoleukodystrophy
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References[edit | edit source]
- ↑ Brul S, Westerveld A, Strijland A, Wanders RJ, Schram AW, Heymans HS, Schutgens RB, Van Den Bosch H, Tager JM. Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. A study using complementation analysis. The Journal of clinical investigation. 1988 Jun 1;81(6):1710-5.
- ↑ Powers JM, Tummons RC, Caviness Jr VS, Moser AB, Moser HW. Structural and chemical alterations in the cerebral maldevelopment of fetal cerebro-hepato-renal (Zellweger) syndrome. Journal of Neuropathology & Experimental Neurology. 1989 May 1;48(3):270-89.
- ↑ Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2012 Sep 1;1822(9):1430-41.
- ↑ Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW. Peroxisome biogenesis disorders. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2006 Dec 1;1763(12):1733-48.
