Peroxisomal disorder

Peroxisomal disorders represent a class of medical conditions caused by defects in peroxisome functions.[1] This may be due to defects in single enzymes[2] important for peroxisome function or in peroxins, proteins encoded by PEX genes that are critical for normal peroxisome assembly and biogenesis.[3]

Peroxisomal disorder
Basic structure of a peroxisome
SpecialtyMedical genetics

Peroxisome biogenesis disorders

Peroxisome biogenesis disorders (PBDs) include the Zellweger syndrome spectrum (PBD-ZSD) and rhizomelic chondrodysplasia punctata type 1 (RCDP1).[4][5] PBD-ZSD represents a continuum of disorders including infantile Refsum disease, neonatal adrenoleukodystrophy, and Zellweger syndrome. Collectively, PBDs are autosomal recessive developmental brain disorders that also result in skeletal and craniofacial dysmorphism, liver dysfunction, progressive sensorineural hearing loss, and retinopathy.[4][5]

PBD-ZSD is most commonly caused by mutations in the PEX1, PEX6, PEX10, PEX12, and PEX26 genes.[6][7] This results in the over-accumulation of very long chain fatty acids and branched chain fatty acids, such as phytanic acid. In addition, PBD-ZSD patients show deficient levels of plasmalogens, ether-phospholipids necessary for normal brain and lung function.

RCDP1 is caused by mutations in the PEX7 gene, which encodes the PTS2 receptor.[8] RCDP1 patients can develop large tissue stores of branched chain fatty acids, such as phytanic acid, and show reduced levels of plasmalogens.

Name OMIM Gene ICD-10
Zellweger syndrome 214100 PEX1, PEX2, PEX3, PEX5, PEX6, PEX12, PEX14, PEX26 Q87.82
Infantile Refsum disease 266510 PEX1, PEX2, PEX26 E80.3
Neonatal adrenoleukodystrophy 202370 PEX5, PEX1, PEX10, PEX13, PEX26 E71.331
RCDP Type 1 215100 PEX7 Q77.3
Heimler syndrome 234580 PEX1, PEX6

Enzyme and transporter defects

Peroxisomal disorders also include:

Name OMIM Gene ICD-10 NA[9]
Pipecolic acidemia 600964 PHYH E80.301
Acatalasia 115500 CAT E80.310
Hyperoxaluria type 1 259900 AGXT E80.311
Acyl-CoA oxidase deficiency 264470 ACOX1 E80.313
D-bifunctional protein deficiency 261515 HSD17B4 E80.314
Dihydroxyacetonephosphate acyltransferase deficiency 222765 GNPAT E80.315
X-linked adrenoleukodystrophy 300100 ABCD1 E71.33
α-Methylacyl-CoA racemase deficiency 604489 AMACR
RCDP Type 2 222765 DHAPAT Q77.3
RCDP Type 3 600121 AGPS Q77.3
Adult Refsum disease-1 266500 PHYH G60.1
Mulibrey nanism 253250 TRIM37

References
  1. Wanders, R. J. A.; Waterham, H. R. (2006). "Biochemistry of Mammalian Peroxisomes Revisited". Annual Review of Biochemistry. 75: 295–332. doi:10.1146/annurev.biochem.74.082803.133329. PMID 16756494.
  2. Wanders, R.; Waterham, H. (2006). "Peroxisomal disorders: the single peroxisomal enzyme deficiencies". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1763 (12): 1707–20. doi:10.1016/j.bbamcr.2006.08.010. PMID 17055078.
  3. Weller, S.; Gould, S. J.; Valle, D. (2003). "Peroxisome Biogenesis Disorders". Annual Review of Genomics and Human Genetics. 4: 165–211. doi:10.1146/annurev.genom.4.070802.110424. PMID 14527301.
  4. Steinberg, S.; Dodt, G.; Raymond, G.; Braverman, N.; Moser, A.; Moser, H. (2006). "Peroxisome biogenesis disorders". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1763 (12): 1733–48. doi:10.1016/j.bbamcr.2006.09.010. PMID 17055079.
  5. Steinberg SJ, Raymond GV, Braverman NE, et al. (2020). Adam MP, Ardinger HH, Pagon RA, et al. (eds.). "Zellweger Spectrum Disorder". GeneReviews® [Internet]. University of Washington. PMID 20301621. NBK1448.
  6. Steinberg, S.; Chen, L.; Wei, L.; Moser, A.; Moser, H.; Cutting, G.; Braverman, N. (2004). "The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum". Molecular Genetics and Metabolism. 83 (3): 252–263. doi:10.1016/j.ymgme.2004.08.008. PMID 15542397.
  7. Yik, W. Y.; Steinberg, S. J.; Moser, A. B.; Moser, H. W.; Hacia, J. G. (2009). "Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders". Human Mutation. 30 (3): E467–E480. doi:10.1002/humu.20932. PMC 2649967. PMID 19105186.
  8. Braverman, N.; Steel, G.; Obie, C.; Moser, A.; Moser, H.; Gould, S. J.; Valle, D. (1997). "Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata". Nature Genetics. 15 (4): 369–376. doi:10.1038/ng0497-369. PMID 9090381. S2CID 33855310.
  9. World Health Organization (7 December 1997). Application of the international classification of diseases to neurology: ICD-NA. World Health Organization. pp. 119–. ISBN 978-92-4-154502-0. Retrieved 23 November 2010.
  • Steinberg SJ, Raymond GV, Braverman NE, et al. (2020). Adam MP, Ardinger HH, Pagon RA, et al. (eds.). "Zellweger Spectrum Disorder". GeneReviews® [Internet]. University of Washington. PMID 20301621. NBK1448.
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