Abstract
The Zellweger spectrum disorders (ZSDs) are known to be severe disorders with onset in the newborn period or later in childhood, frequently resulting in death during childhood or adolescence. Here, we report a case of ZSD due to mutations in the PEX2 gene, with very mild phenotype. A 51-year-old Italian man was referred to us because of a clinical picture characterized by ataxia, areflexia, nystagmus, and strabismus, with childhood onset and slowly progressive course. The patient showed no cognitive impairment. Neurological examination revealed gait ataxia, dysarthria, dysmetria, areflexia, and bilateral pes cavus. Nerve conduction studies indicated a severe axonal sensorimotor polyneuropathy. Brain MRI showed marked cerebellar atrophy and absence of white matter involvement. MR spectroscopy uncovered a decreased N-acetyl aspartate peak. Biochemical analyses suggested a mild peroxisomal defect. Sequence analysis of the PEX2 gene identified two heterozygous mutations. The clinical phenotype of our patient differs from previously reported ZSD patients with PEX2 gene mutations and suggests that genetic screening of PEX2 is warranted in children and adults with otherwise unexplained autosomal recessive ataxia. MRI findings diverged from the “classic” spectrum observed in ZSDs. The moderate impairment in peroxisome biogenesis seems to affect predominantly neuronal cells in cerebellum, leading to cerebellar atrophy.
Competing interests: None declared
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References
Barth PG, Majoie CB, Gootjes J et al (2004) Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival. Neurology 62:439–444
De Stefano N, Narayanan S, Francis GS et al (2001) Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58:65–70
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, Mooijer PA, Gootjes J, Koster J, Wanders RJ, Waterham HR (2011) Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder. Hum Mutat 32:59–69
Girzalsky W, Saffian D, Erdmann R (2010) Peroxisomal protein translocation. Biochim Biophys Acta 1803:724–731
Gootjes J, Mooijer PA, Dekker C et al (2002) Biochemical markers predicting survival in peroxisome biogenesis disorders. Neurology 59:1746–1749
Gootjes J, Elpeleg O, Eyskens F et al (2004) Novel mutations in the PEX2 gene of four unrelated patients with a peroxisome biogenesis disorder. Pediatr Res 55:431–436
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 126:333–338
Régal L, Ebberink MS, Goemans N et al (2010) Mutations in PEX10 are a cause of autosomal recessive ataxia. Ann Neurol 68:259–263
Sevin C, Ferdinandusse S, Waterham HR, Wanders RJ, Aubourg P (2011) Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene. Orphanet J Rare Dis 6:8
Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW (2006) Peroxisome biogenesis disorders. Biochim Biophys Acta 1763:1733–1748
Weller S, Rosewich H, Gärtner J (2008) Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients. J Inherit Metab Dis 31:270–280
Zeharia A, Ebberink MS, Wanders RJ et al (2007) A novel PEX12 mutation identified as the cause of a peroxisomal biogenesis disorder with mild clinical phenotype, mild biochemical abnormalities in fibroblasts and a mosaic catalase immunofluorescence pattern, even at 40 degrees C. J Hum Genet 52:599–606
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Communicated by: Robert Steiner
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Take-Home Message
PEX2 gene mutations can cause Zellweger spectrum disorders with mild phenotype resulting in cerebellar ataxia.
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All authors declare no conflict of interest.
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© 2012 SSIEM and Springer-Verlag Berlin Heidelberg
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Mignarri, A. et al. (2012). Zellweger Spectrum Disorder with Mild Phenotype Caused by PEX2 Gene Mutations. In: JIMD Reports - Case and Research Reports, 2012/3. JIMD Reports, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_102
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DOI: https://doi.org/10.1007/8904_2011_102
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