Article on an Overview of Clinical Features, Peroximal Disorders, Prognosis, Genetic Counseling and Current Treatment Methodologies of Zellweger Syndrome.
Amber Fatima
Government college university, Lahore
Tania Mushtaq
Government college university, Lahore
Sikander Ali
Government college university, Lahore
Receiving Date:
2017-02-19
Acceptance Date:
2017-04-23
Publication Date:
2017-05-20
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Abstract
Zellweger spectrum disorders are the chief subgroup of peroximal biogenesis disorders resulted due to problems in PEX genes. Peroxsoimal biogenesis disorder are resulted due to mutation in well known 13 PEX genes which are used for coding peroxins. The confirmation of peroxisomal biogenesis disorder was done by enzyme analysis and y very long chain fatty acids present in plasma and fibrioblast and also by study of immunoflourescent microscopy. It is one of the well known clinical and biochemical field that is further divided into three clinical phenotypes. It is mainly associated with babies. The defective peroxisomes cause different metabolic disorders which can be mainly perceived in blood and urine. For zellweger syndrome there are no therapies are discovered yet but care and precautions are available. The patients of zellweger syndrome disease have distinct clinacl and facial features, they have short life expectancy mostly upto 1 year.the uses of DNA testing in peroxisomal biogenesis disorder are carrier testing of relatives, testing of parents or genetic preimplantations, diagnosis in families with presence risk of zellweger syndrome disorder and this also help to improve managmentpatients. Sometimes this disease shows misdiagnosis because its symptoms are highly similar to other diseases, so we should perform proper testing to avoid any misleading to any other diseases
Keywords:
Zellweger spectrum disorders; Peroximal Disorders; leukodystrophies
References
- Arai Y, Kitamura Y, Hayashi M, Oshida K, Shimizu T,Yamashiro Y. Effect of dietary Lorenzo‟s oil and docosahexaenoic acid treatment for Zellweger syndrome. CongenitAnom 2008;48:180–182.
- Berendse K, Engelen M, Linthorst GE et al (2014) High prevalence ofprimary adrenal insufficiency in Zellweger spectrum disorders. Orphanet J Rare Dis 9:133
- Bootsma AH, Overmars H, van Rooij A et al (1999) Rapid analysis of conjugated bile acids in plasma using electrospray tandem mass spectrometry: application for selective screening of peroxisomaldisorders.J Inherit Metab Dis 22:307–310
- Bowen P, Lee CS, Zellweger H, Lindenberg R (1964) A familial syndrome ofmultiple congenital defects. Bull Johns HopkinsHosp 114:402–414
- Bowen P, Lee CS, Zellweger H, Lindenberg R. A familialsyndrome of multiple congenital defects. Bull Johns HopkinsHosp 1964;114:402–414.4
- ChaudhryV,MoserHW, Cornblath DR (1996) Nerve conduction studies in adrenomyeloneuropathy. J NeurolNeurosurg Psychiatry 61:181–185
- Dacremont G, Cocquyt G, Vincent G (1995) Measurement of very longchain fatty acids, phytanic and pristanic acid in plasma and cultured fibroblasts by gas chromatography. J InheritMetab Dis 18(Suppl 1):76–83
- Dacremont G, Vincent G (1995) Assay of plasmalogens and polyunsaturated fatty acids (PUFA) in erythrocytes and fibroblasts. J Inherit Metab Dis 18(Suppl 1):84–89
- Ebberink MS, Csanyi B, Chong WK et al (2010) Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene. J Med Genet 47:608–615
- Ebberink MS, Koster J, Visser G et al (2012) A novel defect of peroxisomedivision due to a homozygous non-sense mutation in thePEX11β gene. J Med Genet 49:307–313
- Ebberink MS, Mooijer PAW, Gootjes J et al (2011) Genetic classificationand mutational spectrum ofmore than 600 patients with a Zellweger syndrome spectrum disorder. Hum Mutat 32:59–69
- Einarsson K, Nilsell K, Leijd B, Angelin B (1985) Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N Engl J Med 313:277–282
- Engelen M, van der Kooi AJ, Kemp S et al (2011) X-linkedadrenomyeloneuropathy due to a novel missense mutation in the ABCD1 start codon presenting as demyelinating neuropathy. J
- England JD, Gronseth GS, Franklin G et al (2005) Distal symmetric polyneuropathy: a definition for clinical research: report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 64:199–207
- Ferdinandusse S, Denis S, Dacremont G, Wanders RJA (2009) Toxicity of peroxisomal C27-bile acid intermediates. Mol Genet Metab 96:121–128
- Ferdinandusse S, Houten SM (2006) Peroxisomes and bile acid biosynthesis. BiochimBiophysActa 1763:1427–1440 Ferdinandusse S, Denis S, Mooyer PAW et al (2006) Clinical and biochemical spectrumof D-bifunctional protein deficiency. Ann Neurol 59:92–104
- Foucher J, Chanteloup E, Vergniol J et al (2006) Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 55:403–408
- Gootjes J, Mooijer PAW, Dekker C et al (2002) Biochemical markers predicting survival in peroxisome biogenesis disorders. Neurology 59:1746–1749
- Gould SJ, Raymond GV, Valle D. The peroxisome biogenesisdisorders. In: Scriver CD, Beaudet AL, Sly WS,Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York: McGraw-Hill; 2001: 3181–3218.
- Hiebler S, Masuda T, Hacia JG et al (2014) The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder. Mol Genet Metab 111:522–532
- Kocur I, Resnikoff S (2002) Visual impairment and blindness in Europe and their prevention. Br J Ophthalmol 86:716–722
- Levesque S, Morin C, Guay SP, et al. A founder mutationin the PEX6 gene is responsible for increased incidence ofZellweger syndrome in a French Canadian population.BMC Med Genet 2012;13:72.
- Lines MA, Jobling R, Brady L et al (2014) Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing. Neurology 82:963–996
- Matsui S, FunahashiM, Honda A, Shimozawa N (2013) Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene. Brain Dev 35:842–848
- McMillan HJ, Worthylake T, Schwartzentruber J et al (2012) Specific combination of compound heterozygous mutations in 17β- hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new
- Mignarri A, Vinciguerra C, Giorgio A et al (2012) Zellwegerspectrumdisorder with mild phenotype caused by PEX2 gene mutations.JIMD Rep 6:43–46
- Moser AB, Rasmussen M, Naidu S et al (1995) Phenotype of patients with peroxisomal disorders subdivided into sixteen complementationgroups. J Pediatr 127:13–22
- Moser HW (1999) Genotype-phenotype correlations in disorders of peroxisome biogenesis.Mol Genet Metab 68:316–327
- Peters HB (1961) Vision screening with a Snellen chart. Am J Optom Arch Am AcadOptom 38:487–505
- Pierce SB, Walsh T, Chisholm KM et al (2010) Mutations in the DBPdeficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome.Am J Hum Genet 87:282–288
- Poll-The BT, Gärtner J (2012) Clinical diagnosis, biochemical findings andMRI spectrum of peroxisomaldisorders.BiochimBiophysActa 1822:1421–1429
- Poll-The BT, Gootjes J, Duran M et al (2004) Peroxisome biogenesis disorders with prolonged survival: phenotypic expression in a cohort of 31 patients. Am J Med Genet A 126A:333–338
- Raas-Rothschild A, Wanders RJA, MooijerPAWet al (2002) A PEX6- defective peroxisomal biogenesis disorder with severe phenotype in an infant, versus mild phenotype resembling Usher syndrome in the affected parents.Am J Hum Genet 70:1062–1068
- Shaheen R, Al-Dirbashi OY, Al-Hassnan ZN, et al. Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs. Clin Genet 2011;79:60–70
- Steinberg SJ, Dodt G, Raymond GV, BravermanNE,Moser AB, Moser HW. Peroxisome biogenesis disorders.BiochimBiophysActa 2006;1763:1733–1748.
- Van Asseldonk JTH, Van Den Berg LH, Kalmijn S et al (2005) Criteria for demyelination based on the maximum slowing due to axonal degeneration, determined after warming in water at 37°C: Diagnostic yield in chronic inflammatory demyelinating polyneuropathy. Brain 128:880–891
- Van Geel BM, Koelman JHTM, Barth PG, Ongerboer de Visser BW (1996) Peripheral nerve abnormalities in adrenomyeloneuropathy: a clinical and electrodiagnostic study. Neurology 46:112–118
- VanWoerden CS, GroothoffJW,Wijburg FA et al (2006) High incidence of hyperoxaluria in generalized peroxisomal disorders. Mol Genet Metab 88:346–350
- Vreken P, van Lint AE, Bootsma A et al (1998) Rapid stable isotope dilution analysis of very-long-chain fatty acids, pristanic acid and phytanic acid using gas chromatography–electron impact mass spectrometry. J Chromatogr B Biomed SciAppl 713:281–287
- Wanders RJA, Denis S, Ruiter JP et al (1995a) Measurement of peroxisomal fatty acid beta-oxidation in cultured human skin fibroblasts. J Inherit Metab Dis 18(Suppl 1):113–124
- Wanders RJA, Ofman R, Romeijn GJ, Schutgens RBH (1995b) Measurement of dihydroxyacetone-phosphate acyltransferase (DHAPAT) in chorionic villous samples, blood cells and cultured cells. J Inherit Metab Dis 1:90–100
- Wanders RJA, Wiemer EA, Brul S et al (1989) Prenatal diagnosis of Zellweger syndrome by direct visualization of peroxisomes in chorionic villus fibroblasts by immunofluorescence microscopy. J Inherit Metab Dis 12(Suppl 2):301–304
- Weller S, Gould SJ, Valle D (2003) Peroxisome biogenesis disorders.Annu Rev Genomics Hum Genet 4:165–211
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