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Chapter 37 - Peroxisomal Disorders in Children

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press:  19 January 2021

Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

Peroxisomes are ubiquitous subcellular organelles that are found in essentially all animal and plant cells with the exception of mature anucleated erythrocytes. They carry out many essential biochemical processes, both catabolic and anabolic. Thus, deficiency of numerous peroxisomal proteins essential for structural integrity and metabolic functions causes human disease. These disorders are grouped as either peroxisome biogenesis disorders or isolated peroxisomal protein/enzyme deficiencies. With increased utilization of DNA sequencing as a diagnostic tool, the clinical spectrum of these disorders has expanded, and additional disease genes have been reported. Ultrastructural analysis of hepatic tissue led to the initial association of peroxisomes with human disease. However, not all peroxisomal diseases have liver involvement and thus would not be expected to present to the hepatologist. In this chapter, the focus will be on those diseases in which there is a hepatic component (see Table 37.1).

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Publisher: Cambridge University Press
Print publication year: 2021

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References

Rhodin, J. Correlation of ultrastructural organization and function in normal and experimentally changed proximal tubule cells of the mouse kidney. Thesis, Karolinska Institutet, 1954.Google Scholar
De Duve, C, Baudhuin, P. Peroxisomes (microbodies and related particles). Physiol. Rev 1966;46(2):323–57. doi: 10.1152/physrev.1966.46.2.323Google Scholar
Gabaldón, T. Evolution of the peroxisomal proteome. Subcell Biochem 2018;89:221233. doi: 10.1007/978-981-13-2233-4_9Google Scholar
Ma, C, Agrawal, G, Subramani, S. Peroxisome assembly: matrix and membrane protein biogenesis. J Cell Biol 2011;193(1):716. doi: 10.1083/jcb.201010022Google Scholar
Argyriou, C, D’Agostino, MD, Braverman, N. Peroxisome biogenesis disorders. Transl Sci Rare Dis 2016;1(2):111–44. doi: 10.3233/TRD-160003Google Scholar
Sugiura, A, Mattie, S, Prudent, J, McBride, HM. Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes. Nature 2017;542(7640):251–4. doi: 10.1038/nature21375CrossRefGoogle ScholarPubMed
Schrader, M, Costello, JL, Godinho, LF, Azadi, AS, Islinger, M. Proliferation and fission of peroxisomes – An update. Biochim Biophys Acta 2016;1863(5):971–83. doi: 10.1016/j.bbamcr.2015.09.024Google Scholar
Kunze, M. The type-2 peroxisomal targeting signal. Biochim Biophys Acta Mol Cell Res 2020;1867(2):118609. doi: 10.1016/j.bbamcr.2019.118609CrossRefGoogle ScholarPubMed
Kalel, VC, Erdmann, R. Unraveling of the structure and function of peroxisomal protein import machineries. Subcell Biochem 2018;89:299321. doi: 10.1007/978-981-13-2233-4_13CrossRefGoogle ScholarPubMed
Pedrosa, AG, Francisco, T, Ferreira, MJ, Rodrigues, TA, Barros-Barbosa, A, Azevedo, JE. A mechanistic perspective on PEX1 and PEX6, two AAA+ proteins of the peroxisomal protein import machinery. Int J Mol Sci 2019;20(21). doi: 10.3390/ijms20215246Google Scholar
Nazarko, TY. Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders. Autophagy 2017;13(5):991–4. doi: 10.1080/15548627.2017.1291480Google Scholar
Lazarow, PB, De Duve, C. A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci USA 1976;73(6):2043–6. doi: 10.1073/pnas.73.6.2043Google Scholar
Kemp, S, Theodoulou, FL, Wanders, RJA. Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance. Br J Pharmacol 2011;164(7):1753–66. doi: 10.1111/j.1476-5381.2011.01435.xGoogle Scholar
Ferdinandusse, S, et al. ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism.J Med Genet 2017;54(5):330–7. doi: 10.1136/jmedgenet-2016-104132Google Scholar
Kemp, S, et al. Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy. Nat Med 1998;4(11):1261–8. doi: 10.1038/3242CrossRefGoogle ScholarPubMed
Wanders, RJA. Metabolic functions of peroxisomes in health and disease. Biochimie 2014;98:3644. doi: 10.1016/j.biochi.2013.08.022Google Scholar
Houten, SM, et al. Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids. J Lipid Res 2012;53(7):1296–303. doi: 10.1194/jlr.M024463Google Scholar
Korman, SH, Mandel, H, Gutman, A. Characteristic urine organic acid profile in peroxisomal biogenesis disorders. J Inherit Metab Dis 2000;23(4):425–8. doi: 10.1023/a:1005624523611CrossRefGoogle ScholarPubMed
Wanders, RJA, Ferdinandusse, S, Brites, P, Kemp, S. Peroxisomes, lipid metabolism and lipotoxicity. Biochim Biophys Acta 2010;1801(3):272–80. doi: 10.1016/j.bbalip.2010.01.001Google Scholar
Steinberg, SJ, Dodt, G, Raymond, GV, Braverman, NE, Moser, AB, Moser, HW. Peroxisome biogenesis disorders. Biochim Biophys Acta 2006;1763(12):1733–48. doi: 10.1016/j.bbamcr.2006.09.010Google Scholar
Ferdinandusse, S, et al. Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy.Am J Hum Genet 2006;78(6):1046–52. doi: 10.1086/503921CrossRefGoogle ScholarPubMed
Moore, SA, Hurt, E, Yoder, E, Sprecher, H, Spector, AA. Docosahexaenoic acid synthesis in human skin fibroblasts involves peroxisomal retroconversion of tetracosahexaenoic acid. J Lipid Res 1995;36(11):2433–43.Google Scholar
Wanders, RJA, Komen, J, Ferdinandusse, S. Phytanic acid metabolism in health and disease. Biochim Biophys Acta 2011;1811(9):498507. doi: 10.1016/j.bbalip.2011.06.006Google Scholar
Ferdinandusse, S, et al. A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum Mol Genet 2015;24(2):361–70. doi: 10.1093/hmg/ddu448Google Scholar
Watkins, PA. Very-long-chain acyl-CoA synthetases. J Biol Chem 2008;283(4):1773–7. doi: 10.1074/jbc.R700037200Google Scholar
de Aguiar Vallim, TQ, Tarling, EJ, Edwards, PA. Pleiotropic roles of bile acids in metabolism. Cell Metab 2013;17(5):657–69. doi: 10.1016/j.cmet.2013.03.013Google Scholar
Kovacs, WJ, et al. Localization of the pre-squalene segment of the isoprenoid biosynthetic pathway in mammalian peroxisomes. Histochem Cell Biol 2007;127(3):273–90. doi: 10.1007/s00418-006-0254-6Google Scholar
Weinhofer, I, Kunze, M, Stangl, H, Porter, FD, Berger, J. Peroxisomal cholesterol biosynthesis and Smith-Lemli-Opitz syndrome. Biochem Biophys Res Commun 2006;345(1):205–9. doi: 10.1016/j.bbrc.2006.04.078Google Scholar
Hogenboom, S, Tuyp, JJM, Espeel, M, Koster, J, Wanders, RJA, Waterham, HR. Mevalonate kinase is a cytosolic enzyme in humans. J Cell Sci 2004;117(4):631–9. doi: 10.1242/jcs.00910CrossRefGoogle ScholarPubMed
Hogenboom, S, Tuyp, JJM, Espeel, M, Koster, J, Wanders, RJA, Waterham, HR. Phosphomevalonate kinase is a cytosolic protein in humans. J Lipid Res 2004;45(4):697705. doi: 10.1194/jlr.M300373-JLR200Google Scholar
Hogenboom, S, Tuyp, JJM, Espeel, M, Koster, J, Wanders, RJA, Waterham, HR. Human mevalonate pyrophosphate decarboxylase is localized in the cytosol. Mol Genet Metab 2004;81(3):216–24. doi: 10.1016/j.ymgme.2003.12.001CrossRefGoogle ScholarPubMed
Lloyd, MD, Darley, DJ, Wierzbicki, AS, Threadgill, MD. Alpha-methylacyl-CoA racemase: an “obscure” metabolic enzyme takes centre stage. FEBS J 2008;275(6):1089–102. doi: 10.1111/j.1742-4658.2008.06290.xGoogle Scholar
Van Veldhoven, PP, Croes, K, Asselberghs, S, Herdewijn, P, Mannaerts, GP. Peroxisomal beta-oxidation of 2-methyl-branched acyl-CoA esters: stereospecific recognition of the 2S-methyl compounds by trihydroxycoprostanoyl-CoA oxidase and pristanoyl-CoA oxidase. FEBS Lett 1996;388(1):80–4. doi: 10.1016/0014-5793(96)00508-xGoogle Scholar
Horrocks, LA, Sharma, M. (1982). Plasmalogens and O-alkyl glycerophospholipids in Phospholipids. In Nawthorne, JN, Ansell, GB, (Eds.), Phospholipids. New Comprehensive Biochemistry (pp. 5193). Amsterdam: Elsevier Biomedical Press.Google Scholar
Honsho, M, Fujiki, Y. Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals. FEBS Lett 2017;591(18):2720–9. doi: 10.1002/1873-3468.12743CrossRefGoogle ScholarPubMed
Mannaerts, GP, Van Veldhoven, PP, Casteels, M. Peroxisomal lipid degradation via beta- and alpha-oxidation in mammals. Cell Biochem Biophys 2000;32:7387. doi:10.1385/cbb:32:1-3:73Google Scholar
Williams, EL, et al. Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene. Hum Mutat 2009;30(6):910–17. doi: 10.1002/humu.21021Google Scholar
van Woerden, CS, et al. High incidence of hyperoxaluria in generalized peroxisomal disorders. Mol Genet Metab 2006;88(4):346–50. doi: 10.1016/j.ymgme.2006.03.004Google Scholar
Zaar, K, Angermüller, S, Völkl, A, Fahimi, HD. Pipecolic acid is oxidized by renal and hepatic peroxisomes. Implications for Zellweger’s cerebro-hepato-renal syndrome (CHRS). Exp Cell Res 1986;164(1):267–71. doi: 10.1016/0014-4827(86)90475-1Google Scholar
Frerman, FE, Goodman, SI. (1995). Nuclear-encoded defects of the mitochondrial respiratory chain, including glutaric acidemia type II. In Shriver, CR, Beaudet, AL, Sly, WS and Valle, D (Eds.), The Metabolic and Molecular Bases of Inherited Disease, 7th Ed., pp. 1611–29. McGraw-Hill: New York.Google Scholar
Crowther, LM, Mathis, D, Poms, M, Plecko, B. New insights into human lysine degradation pathways with relevance to pyridoxine-dependent epilepsy due to antiquitin deficiency. J Inherit Metab Dis 2019;42(4):620–8. doi: 10.1002/jimd.12076Google Scholar
Fransen, M, Lismont, C. Peroxisomes and cellular oxidant/antioxidant balance: protein redox modifications and impact on inter-organelle communication. Subcell Biochem 2018;89:435–61. doi: 10.1007/978-981-13-2233-4_19CrossRefGoogle ScholarPubMed
Wanders, RJA, Klouwer, FCC, Ferdinandusse, S, Waterham, HR, Poll-Thé, BT. Clinical and laboratory diagnosis of peroxisomal disorders. Methods Mol Biol Clifton NJ 2017;1595:329–42. doi: 10.1007/978-1-4939-6937-1_30Google Scholar
Braverman, NE, et al. Peroxisome biogenesis disorders in the Zellweger spectrum: an overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab 2016;117(3):313–21. doi: 10.1016/j.ymgme.2015.12.009Google Scholar
Peduto, A, et al. Hyperpipecolic acidaemia: a diagnostic tool for peroxisomal disorders. Mol Genet Metab 2004;82(3):224–30. doi: 10.1016/j.ymgme.2004.04.010Google Scholar
De Biase, I, et al. Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2020;22(4):686–97. doi: 10.1038/s41436-019-0713-9Google Scholar
Ferdinandusse, S, Houten, SM. Peroxisomes and bile acid biosynthesis. Biochim Biophys Acta 2006;1763(12):1427–40. doi: 10.1016/j.bbamcr.2006.09.001Google ScholarPubMed
Hubbard, WC, et al. Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method.Mol Genet Metab 2009;97(3):212–20. doi: 10.1016/j.ymgme.2009.03.010Google Scholar
Kemper, AR, et al. Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation. Genet Med 2017;19(1):121–6. doi: 10.1038/gim.2016.68Google Scholar
Ferdinandusse, S, Ebberink, MS, Vaz, FM, Waterham, HR, Wanders, RJA. The important role of biochemical and functional studies in the diagnostics of peroxisomal disorders. J Inherit Metab Dis 2016;39(4):531–43. doi: 10.1007/s10545-016-9922-4CrossRefGoogle ScholarPubMed
Berendse, K, et al. Zellweger spectrum disorders: clinical manifestations in patients surviving into adulthood. J Inherit Metab Dis 2016;39(1):93106. doi: 10.1007/s10545-015-9880-2Google Scholar
Falkenberg, KD, et al. Allelic expression imbalance promoting a mutant PEX6 allele causes Zellweger spectrum disorder. Am J Hum Genet 2017;101(6):965–76. doi: 10.1016/j.ajhg.2017.11.007Google Scholar
Steinberg, S, et al. The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. Mol Genet Metab 2004;83(3):252–63. doi: 10.1016/j.ymgme.2004.08.008Google Scholar
Shimozawa, N, Nagase, T, Takemoto, Y, Ohura, T, Suzuki, Y, Kondo, N. Genetic heterogeneity of peroxisome biogenesis disorders among Japanese patients: evidence for a founder haplotype for the most common PEX10 gene mutation. Am J Med Genet A 2003;120(1):40–3. doi: 10.1002/ajmg.a.20030Google Scholar
Levesque, S, et al. A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. BMC Med Genet 2012;13:72. doi: 10.1186/1471-2350-13-72Google Scholar
Yik, WY, Steinberg, SJ, Moser, AB, Moser, HW, Hacia, JG. Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Hum Mutat 2009;30(3):E467480. doi: 10.1002/humu.20932Google Scholar
Wiedemann, HR. Hans-Ulrich Zellweger (1909–1990). Eur J Pediatr 1991;150(7):451. doi: 10.1007/bf01958418CrossRefGoogle ScholarPubMed
Govaerts, L, Monnens, L, Tegelaers, W, Trijbels, F, van Raay-Selten, A. Cerebro-hepato-renal syndrome of Zellweger: clinical symptoms and relevant laboratory findings in 16 patients. Eur J Pediatr 1982;139(2):125–8. doi: 10.1007/bf00441495CrossRefGoogle ScholarPubMed
Smith, DW, Opitz, JM, Inhorn, SL. A syndrome of multiple developmental defects including polycystic kidneys and intrahepatic biliary dysgenesis in 2 siblings. J Pediatr 1965;67(4):617–24. doi: 10.1016/s0022-3476(65)80433-4Google Scholar
Gilchrist, KW, Gilbert, EF, Shahidi, NT, Opitz, JM. The evaluation of infants with the Zellweger (cerebro-hepato-renal) syndrome. Clin Genet 1975;7(5):413–16. doi: 10.1111/j.1399-0004.1975.tb00350.xGoogle Scholar
Barkovich, AJ, Peck, WW. MR of Zellweger syndrome. AJNR Am J Neuroradiol 1997;18(6):1163–70.Google ScholarPubMed
Berendse, K, Engelen, M, Linthorst, GE, van Trotsenburg, ASP, Poll, BT. The High prevalence of primary adrenal insufficiency in Zellweger spectrum disorders. Orphanet J Rare Dis 2014;9:133. doi: 10.1186/s13023-014-0133-5Google Scholar
Weller, S, Rosewich, H, Gärtner, J. Cerebral MRI as a valuable diagnostic tool in Zellweger spectrum patients. J Inherit Metab Dis 2008;31:270–80. doi: 10.1007/s10545-008-0856-3Google Scholar
Rush, ET, Goodwin, JL, Braverman, NE, Rizzo, WB. Low bone mineral density is a common feature of Zellweger spectrum disorders. Mol Genet Metab 2016;117(1):33–7. doi: 10.1016/j.ymgme.2015.11.009CrossRefGoogle ScholarPubMed
Ratbi, I, et al. Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. Am J Hum Genet 2015;97(4):535–45. doi: 10.1016/j.ajhg.2015.08.011Google Scholar
Majewski, J, et al. A new ocular phenotype associated with an unexpected but known systemic disorder and mutation: novel use of genomic diagnostics and exome sequencing. J Med Genet 2011;48(9):593–6. doi: 10.1136/jmedgenet-2011-100288Google Scholar
Simons, J. Phenotypic variability in fraternal twins with PEX1 mutations: Zellweger syndrome with discordant clinical phenotype. Hered Genet 2013;2(1). doi: 10.4172/2161-1041.S5-001Google Scholar
Klouwer, FCC, Berendse, K, Ferdinandusse, S, Wanders, RJA, Engelen, M, Poll BT., The Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis 2015;10:151. doi: 10.1186/s13023-015-0368-9Google Scholar
Sevin, C, Ferdinandusse, S, Waterham, HR, Wanders, RJ, Aubourg, P. Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene. Orphanet J Rare Dis 2011;6:8. doi: 10.1186/1750-1172-6-8Google Scholar
Zhang, C, et al. Ataxia with novel compound heterozygous PEX10 mutations and a literature review of PEX10-related peroxisome biogenesis disorders. Clin Neurol Neurosurg 2019;177:92–6. doi: 10.1016/j.clineuro.2019.01.004CrossRefGoogle Scholar
Gootjes, J, Skovby, F, Christensen, E, Wanders, RJA, Ferdinandusse, S. Reinvestigation of trihydroxycholestanoic acidemia reveals a peroxisome biogenesis disorder. Neurology 2004;62(11):2077–81. doi: 10.1212/01.wnl.0000127576.26352.d1Google Scholar
Ebberink, MS et al. Identification of an unusual variant peroxisome biogenesis disorder caused by mutations in the PEX16 gene. J Med Genet 2010;47(9):608–15. doi: 10.1136/jmg.2009.074302Google Scholar
Bacino, C, et al. A homozygous mutation in PEX16 identified by whole-exome sequencing ending a diagnostic odyssey. Mol Genet Metab 2015;5:1518. doi: 10.1016/j.ymgmr.2015.09.001Google Scholar
Steinberg, SJ, et al. A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts. J Inherit Metab Dis 2009;32(1):109–19. doi: 10.1007/s10545-008-0969-8Google Scholar
Pineda, M, et al. Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism. J Child Neurol 1999;14(7):434–9. doi: 10.1177/088307389901400705Google Scholar
Powers, JM, et al. Fetal cerebrohepatorenal (Zellweger) syndrome: dysmorphic, radiologic, biochemical, and pathologic findings in four affected fetuses. Hum Pathol 1985;16(6):610–20. doi: 10.1016/s0046-8177(85)80111-8Google Scholar
Maeda, K, et al. Oral bile acid treatment in two Japanese patients with Zellweger syndrome. J Pediatr Gastroenterol Nutr 2002;35(2):227–30. doi: 10.1097/00005176-200208000-00025CrossRefGoogle ScholarPubMed
Lee, H.-F., Mak, S, Chi, C-S, Huang, C-S. Zellweger syndrome: report of one case. Acta Paediatr Tw 2001;42:53–6.Google ScholarPubMed
Setchell, KDR, et al. Oral bile acid treatment and the patient with Zellweger syndrome. Hepatology 1992;15(2):198207. doi: 10.1002/hep.1840150206CrossRefGoogle ScholarPubMed
Danks, DM, Tippett, P, Adams, C, Campbell, P. Cerebro-hepato-renal syndrome of Zellweger. J Pediatr 1975;86(3):382–7.Google Scholar
Vamecq, J, et al. Multiple peroxisomal enzymatic deficiency disorders. Am J Pathol 1986;125(3):12.Google Scholar
Brun, A, Gilboa, M, Meeuwisse, GW, Nordgren, H. The Zellweger syndrome: subcellular pathology, neuropathology, and the demonstration of pneumocystis carinii pneumonitis in two siblings. Eur J Pediatr 1978;127(4):229–45. doi: 10.1007/BF00493539CrossRefGoogle ScholarPubMed
Muller-Hocker, J, Walther, JU, Bise, K, Pongratz, D, Hubner, G. Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study. Cell Pathol 1984;45:125–38.Google Scholar
Wilson, GN, et al. Zellweger syndrome: diagnostic assays, syndrome delineation, and potential therapy. Am J Med Genet 1986;24(1):6982. doi: 10.1002/ajmg.1320240109Google Scholar
Nakada, Y, et al. A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein. Brain Dev 1993;15(6):453–6. doi: 10.1016/0387-7604(93)90087-OGoogle Scholar
Jaruratanasirikul, S, Vanskinanont, P, Saetung, P, Mitarnun, W. Zellweger syndrome: first reported case in Thailand and literature review. Southeast Asian J. Trop. Med. Public Health 1995;26(Suppl. 1):4751.Google Scholar
Huybrechts, SJ, et al. Identification of a novel PEX14 mutation in Zellweger syndrome. BMJ Case Rep 2009;2009. doi: 10.1136/bcr.07.2008.0503CrossRefGoogle ScholarPubMed
Gilchrist, KW, Gilbert, EF, Goldfarb, S, Goll, U, Spranger, JW, Opitz, JM. Studies of malformation syndromes of man XIB: the cerebro-hepato-renal syndrome of zellweger: comparative pathology. Eur J Pediatr 1976;121(2):99118. doi: 10.1007/BF00443065Google Scholar
Chow, CW, Poulos, A, Fellenberg, AJ, Christodoulou, J, Danks, DM. Autopsy findings in two siblings with infantile Refsum disease. Acta Neuropathol 1992;83(2):190–5. doi: 10.1007/BF00308478Google Scholar
Hughes, JL, et al. Pathology of hepatic peroxisomes and mitochondria in patients with peroxisomal disorders. Virchows Arch A Pathol Anat Histopathol 1990;416(3):255–64. doi: 10.1007/BF01678985CrossRefGoogle ScholarPubMed
Scotto, JM, et al. Infantile phytanic acid storage disease, a possible variant of Refsum’s disease: three cases, including ultrastructural studies of the liver. J Inherit Metab Dis 1982;5(2):8390. doi: 10.1007/BF01799998Google Scholar
Torvik, A, Torp, S, Kase, BF, EK, J, Skjeldal, O, Stokke, O. Infantile Refsum’s disease: a generalized peroxisomal disorder case report with postmortem examination. J Neurol Sci 1988;85:3953.CrossRefGoogle ScholarPubMed
Nakamura, K, et al. Cerebro-hepato-renal syndrome of Zellweger. Pathol Int 1986;36(11): 1727–35. doi: 10.1111/j.1440-1827.1986.tb02236.xGoogle Scholar
Warren, M, Mierau, G, Wartchow, EP, Shimada, H, Yano, S. Histologic and ultrastructural features in early and advanced phases of Zellweger spectrum disorder (infantile Refsum disease). Ultrastruct Pathol 2018;42(3):220–7. doi: 10.1080/01913123.2018.1440272CrossRefGoogle ScholarPubMed
Berendse, K, et al. Hepatic symptoms and histology in 13 patients with a Zellweger spectrum disorder. J Inherit Metab Dis 2019;42(5):955–65. doi: 10.1002/jimd.12132Google Scholar
Komatsuzaki, S, et al. First Japanese case of Zellweger syndrome with a mutation in PEX14. Pediatr Int Off J Jpn Pediatr Soc 2015;57(6):1189–92. doi: 10.1111/ped.12713Google Scholar
Bjørgo, K, et al. Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder. Mol Genet Metab 2017;121(4):325–8. doi: 10.1016/j.ymgme.2017.06.004Google Scholar
Heubi, JE, Setchell, KDR, Bove, KE. Long-term cholic acid therapy in Zellweger spectrum disorders. Case Rep Gastroenterol 2018;12(2):360–72. doi: 10.1159/000490095Google Scholar
Budden, SS, Kennaway, NG, Buist, NRM, Poulos, A, Weleber, RG. Dysmorphic syndrome with phytanic acid oxidase deficiency, abnormal very long chain fatty acids, and pipecolic acidemia: studies in four children. J Pediatr 1986;108(1):33–9. doi: 10.1016/S0022-3476(86)80765-XGoogle Scholar
Das, AK, Holmes, RD, Wilson, GN, Hajra, AK. Dietary ether lipid incorporation into tissue plasmalogens of humans and rodents. Lipids 1992;27(6):401–5. doi: 10.1007/BF02536379Google Scholar
Sani, MN, Ahmadi, M, Roohani, P, Rezaei, N. Early onset hepatocellular disease in an infant with Zellweger syndrome. Acta Med Iran 2015;53(10):656–8.Google Scholar
Heubi, JE, Bishop, WP. Long-term cholic acid treatment in a patient with Zellweger spectrum disorder. Case Rep Gastroenterol 2018;12(3):661–70. doi: 10.1159/000494555Google Scholar
Roels, F, Espeel, M, De Craemer, D. Liver pathology and immunocytochemistry in congenital peroxisomal diseases: a review. J Inherit Metab Dis 1991;14(6):853–75. doi: 10.1007/BF01800464Google Scholar
Roels, F, Espeel, M, Poggi, F, Mandel, H, Van Maldergem, L, Saudubray, JM. Human liver pathology in peroxisomal diseases: a review including novel data. Biochimie 1993;75(3–4):281–92. doi: 10.1016/0300-9084(93)90088-AGoogle Scholar
Mooi, WJ, Dingemans, KP, Van Den Bergh Weerman, MA, Jobsis, AC, Heymans, HSA, Barth, PG. Ultrastructure of the liver in the cerebrohepatorenal syndrome of Zellweger. Ultrastruct Pathol 1983;5(2–3):135–44. doi: 10.3109/01913128309141833Google Scholar
Kerckaert, I, Dingemans, KP, Heymans, HSA, Vamecq, J, Roels, F. Polarizing inclusions in some organs of children with congenital peroxisomal diseases (Zellweger’s, Refsum’s, chondrodysplasia punctata (rhizomelic form), X-linked adrenoleukodystrophy). J Inherit Metab Dis 1988;11(4):372–86. doi: 10.1007/BF01800426Google Scholar
Poll, BT, et al. A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). Am J Hum Genet 1988;42(3):422–34.Google Scholar
Ferdinandusse, S, et al. Clinical, biochemical, and mutational spectrum of peroxisomal acyl–coenzyme A oxidase deficiency. Hum Mutat 2007;28(9):904–12. doi: 10.1002/humu.20535Google Scholar
Carrozzo, R, et al. Peroxisomal acyl-CoA-oxidase deficiency: two new cases. Am J Med Genet A 2008;146A(13):1676–81. doi: 10.1002/ajmg.a.32298Google Scholar
Ferdinandusse, S, et al. Adult peroxisomal acyl-coenzyme A oxidase deficiency with cerebellar and brainstem atrophy. J Neurol Neurosurg Psychiatry 2010;81(3):310–12. doi: 10.1136/jnnp.2009.176255Google Scholar
Ferdinandusse, S, et al. A novel case of ACOX2 deficiency leads to recognition of a third human peroxisomal acyl-CoA oxidase. Biochim Biophys Acta BBA – Mol Basis Dis 2018;1864(3):952–8. doi: 10.1016/j.bbadis.2017.12.032Google Scholar
Monte, MJ, et al. ACOX2 deficiency: an inborn error of bile acid synthesis identified in an adolescent with persistent hypertransaminasemia. J Hepatol 2017;66(3):581–8. doi: 10.1016/j.jhep.2016.11.005Google Scholar
Vilarinho, S, et al. ACOX2 deficiency: a disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment. Proc Natl Acad Sci 2016;113(40):11289–93. doi: 10.1073/pnas.1613228113Google Scholar
Ghirri, P, et al. A case of d-bifunctional protein deficiency: clinical, biochemical and molecular investigations: a severe case of DBP deficiency. Pediatr Int 2011;53(4):583–7. doi: 10.1111/j.1442-200X.2010.03255.xGoogle Scholar
Suzuki, Y, et al. d-3-Hydroxyacyl-CoA dehydratase/d-3-hydroxyacyl-coa dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder. Am J Hum Genet 1997;61(5):1153–62. doi: 10.1086/301599Google Scholar
Mizumoto, H, et al. Mild case of d-bifunctional protein deficiency associated with novel gene mutations: letter to the editor. Pediatr Int 2012; 54(2):303–4. doi: 10.1111/j.1442-200X.2012.03562.xGoogle Scholar
Khan, A, Wei, XC, Snyder, FF, Mah, JK, Waterham, H, Wanders, RJA. Neurodegeneration in D-bifunctional protein deficiency: diagnostic clues and natural history using serial magnetic resonance imaging. Neuroradiology 2010;52(12):1163–6. doi: 10.1007/s00234-010-0768-4Google Scholar
Grønborg, S, et al. Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma. Am J Med Genet A 2010;152A(11):2845–9. doi: 10.1002/ajmg.a.33677Google Scholar
Ferdinandusse, S, et al. Clinical and biochemical spectrum of D-bifunctional protein deficiency. Ann. Neurol 2006;59(1):92104. doi: 10.1002/ana.20702Google Scholar
Nascimento, J, et al. D-Bifunctional protein deficiency: a cause of neonatal onset seizures and hypotonia.Pediatr Neurol 2015;52(5):539–43. doi: 10.1016/j.pediatrneurol.2015.01.007Google Scholar
Matsukawa, T, et al. Slowly progressive d -bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing. J Neurol Sci 2017;372:610. doi: 10.1016/j.jns.2016.11.009Google Scholar
Ferdinandusse, S, et al. Mutational spectrum of d-bifunctional protein deficiency and structure-based genotype-phenotype analysis. Am J Hum Genet 2006;78(1):112–24. doi: 10.1086/498880Google Scholar
Soorani-Lunsing, RJ, et al. Normal very-long-chain fatty acids in peroxisomal D-bifunctional protein deficiency: a diagnostic pitfall. J Inherit Metab Dis 2005;28(6):1172–4. doi: 10.1007/s10545-005-0149-zGoogle Scholar
Lines, MA, et al. Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing. Neurology 2014;82(11):963–8. doi: 10.1212/WNL.0000000000000219Google Scholar
Amor, DJ, et al. Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. Neurol Genet 2016;2(6):e114. doi: 10.1212/NXG.0000000000000114Google Scholar
McMillan, HJ, et al. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. Orphanet J Rare Dis 2012;7:90. doi: 10.1186/1750-1172-7-90Google Scholar
Verhagen, JMA, et al. Incidental finding of alpha-methylacyl-CoA racemase deficiency in a patient with oculocutaneous albinism type 4. Am J Med Genet A 2012;158A(11):2931–4. doi: 10.1002/ajmg.a.35611Google Scholar
Ferdinandusse, S, et al. Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet 2000;24(2):188–91. doi: 10.1038/72861Google Scholar
Setchell, KDR, et al. Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy. Gastroenterology 2003;124(1):217–32. doi: 10.1053/gast.2003.50017Google Scholar
Dick, D, Horvath, R, Chinnery, PF. AMACR mutations cause late-onset autosomal recessive cerebellar ataxia. Neurology 2011;76(20):1768–70. doi: 10.1212/WNL.0b013e31821a4484Google Scholar
Clarke, CE, et al. Tremor and deep white matter changes in alpha-methylacyl-CoA racemase deficiency. Neurology 2004;63(1):188–9. doi: 10.1212/01.wnl.0000132841.81250.b7Google Scholar
Thompson, SA, Calvin, J, Hogg, S, Ferdinandusse, S, Wanders, RJA, Barker, RA. Relapsing encephalopathy in a patient with α-methylacyl-CoA racemase deficiency. BMJ Case Rep 2009;2009:bcr08.2008.0814. doi: 10.1136/bcr.08.2008.0814Google Scholar
Kapina, V, et al. Relapsing rhabdomyolysis due to peroxisomal alpha-methylacyl-coa racemase deficiency. Neurology 2010;75(14):1300–2. doi: 10.1212/WNL.0b013e3181f612a5Google Scholar
Haugarvoll, K, et al. MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing. Orphanet J Rare Dis 2013;8(1):1. doi: 10.1186/1750-1172-8-1Google Scholar
Setchell, KDR, et al. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology 2013;144(5):945–55.e6. doi: 10.1053/j.gastro.2013.02.004Google Scholar
Hadžić, N, Bull, LN, Clayton, PT, Knisely, AS. Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency. World J Gastroenterol 2012;18(25):3322–6. doi: 10.3748/wjg.v18.i25.3322Google Scholar
Chong, CPK, et al. Bile acid-CoA ligase deficiency – a new inborn error of bile acid metabolism. J Inherit Metab Dis 2012;35(3)521–30. doi: 10.1007/s10545-011-9416-3CrossRefGoogle ScholarPubMed
Heubi, JE, et al. Treatment of bile acid amidation defects with glycocholic acid. Hepatology 2015;61(1):268–74. doi: 10.1002/hep.27401Google Scholar
Baes, M, Van Veldhoven, PP. Mouse models for peroxisome biogenesis defects and β-oxidation enzyme deficiencies. Biochim Biophys Acta BBA – Mol Basis Dis 2012;1822(9):14891500. doi: 10.1016/j.bbadis.2012.03.003Google Scholar
Keane, MH, et al. Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice. Hepatology 2007;45(4):982–97. doi: 10.1002/hep.21532Google Scholar
Krysko, O, et al. Neocortical and cerebellar developmental abnormalities in conditions of selective elimination of peroxisomes from brain or from liver. J Neurosci Res 2007;85(1):5872. doi: 10.1002/jnr.21097Google Scholar
Dirkx, R, et al. Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities. Hepatology 2005;41(4):868–78. doi: 10.1002/hep.20628Google Scholar
Li, X, Baumgart, E, Morrell, JC, Jimenez-Sanchez, G, Valle, D, Gould, SJ. PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function. Mol Cell Biol 2002;22(12):4358–65. doi: 10.1128/mcb.22.12.4358-4365.2002Google Scholar
Li, X, et al. PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation. Mol Cell Biol 2002;22(23):8226824000000000000. doi: 10.1128/mcb.22.23.8226-8240.2002Google Scholar
Weng, H, et al. Pex11α deficiency impairs peroxisome elongation and division and contributes to nonalcoholic fatty liver in mice. Am J Physiol Endocrinol Metab 2012; 304(2): E187E196. doi: 10.1152/ajpendo.00425.2012Google Scholar
Hiebler, S, et al. The Pex1-G844D mouse: a model for mild human Zellweger spectrum disorder. Mol Genet Metab 2014;111(4):522–32. doi: 10.1016/j.ymgme.2014.01.008Google Scholar
Berendse, K, et al. Liver disease predominates in a mouse model for mild human Zellweger spectrum disorder. Biochim Biophys Acta BBA – Mol Basis Dis 2019;1865(10):2774–87. doi: 10.1016/j.bbadis.2019.06.013Google Scholar
Fan, CY, et al. Targeted disruption of the peroxisomal fatty acyl-Coa oxidase gene: generation of a mouse model of pseudoneonatal adrenoleukodystrophya. Ann NY Acad Sci 1996;804(1):530–41. doi: 10.1111/j.1749-6632.1996.tb18643.xGoogle Scholar
Fan, CY, Pan, J, Usuda, N, Yeldandi, AV, Rao, MS, Reddy, JK. Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism. J Biol Chem 1998;273(25):15639–45. doi: 10.1074/jbc.273.25.15639Google Scholar
Huang, J, et al. Progressive endoplasmic reticulum stress contributes to hepatocarcinogenesis in fatty acyl-Coa oxidase 1–deficient mice. Am J Pathol 2011;179(2):703–13. doi: 10.1016/j.ajpath.2011.04.030Google Scholar
Baes, M, et al. Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. J Biol Chem 2000;275(21)16329–36. doi: 10.1074/jbc.M001994200Google Scholar
Ferdinandusse, S, et al. Developmental changes of bile acid composition and conjugation in l- and d-bifunctional protein single and double knockout mice. J Biol Chem 2005;280(19):18658–66. doi: 10.1074/jbc.M414311200Google Scholar
Savolainen, K, et al. A mouse model for α-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids. Hum Mol Genet 2004;13(9):955–65. doi: 10.1093/hmg/ddh107Google Scholar
Selkälä, EM, et al. Metabolic adaptation allows Amacr-deficient mice to remain symptom-free despite low levels of mature bile acids. Biochim Biophys Acta BBA – Mol Cell Biol Lipids 2013;1831(8):1335–43. doi: 10.1016/j.bbalip.2013.05.002Google Scholar
Rogers, AB, Dintzis, RZ (2012). Liver and gallbladder, in Comparative Anatomy and Histology (pp. 193201). Philadelphia, PA: Elsevier.Google Scholar
Ferdinandusse, S, Denis, S, Dacremont, G, Wanders, RJA. Toxicity of peroxisomal C27-bile acid intermediates. Mol Genet Metab 2009;96(3):121–8. doi: 10.1016/j.ymgme.2008.11.165Google Scholar
Peeters, A, et al. Carbohydrate metabolism is perturbed in peroxisome-deficient hepatocytes due to mitochondrial dysfunction, amp-activated protein kinase (ampk) activation, and peroxisome proliferator-activated receptor γ coactivator 1α (pgc-1α) suppression. J Biol Chem 2011;286(49):42162–79. doi: 10.1074/jbc.M111.299727Google Scholar
Peeters, A, Swinnen, JV, Van Veldhoven, PP, Baes, M. Hepatosteatosis in peroxisome deficient liver despite increased β-oxidation capacity and impaired lipogenesis. Biochimie 2011;93(10):1828–38. doi: 10.1016/j.biochi.2011.06.034Google Scholar
Kovacs, WJ, et al. Peroxisome deficiency-induced ER stress and SREBP-2 pathway activation in the liver of newborn PEX2 knock-out mice. Biochim Biophys Acta 2012;1821(6):895907. doi: 10.1016/j.bbalip.2012.02.011Google Scholar
Martens, K, et al. Coordinate induction of PPARα and SREBP2 in multifunctional protein 2 deficient mice. Biochim Biophys Acta BBA – Mol Cell Biol Lipids 2008;1781(11):694702. doi: 10.1016/j.bbalip.2008.07.010Google Scholar
Hashimoto, T, et al. Peroxisomal and mitochondrial fatty acid beta-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor alpha and peroxisomal fatty acyl-CoA oxidase. Genotype correlation with fatty liver phenotype. J Biol Chem 1999;274(27):19228–36. doi: 10.1074/jbc.274.27.19228Google Scholar
Faust, PL, Kovacs, WJ. Cholesterol biosynthesis and ER stress in peroxisome deficiency. Biochimie 2014;98:7585. doi: 10.1016/j.biochi.2013.10.019Google Scholar
Mackie, JT, Atshaves, BP, Payne, HR, McIntosh, AL, Schroeder, F, Kier, AB. Phytol-induced hepatotoxicity in mice. Toxicol Pathol 2009;37(2):201–8. doi: 10.1177/0192623308330789Google Scholar
Cattley, RC, Popp, JA (2002). Liver, in Handbook of Toxicologic Pathology, 2nd Ed., (pp. 187–214). San Diego: Academic Press.Google Scholar
Gonzalez, FJ, Shah, YM. PPARα: Mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicology 2008;246(1)28. doi: 10.1016/j.tox.2007.09.030Google Scholar
Zeynelabidin, S, et al. Coagulopathy in Zellweger spectrum disorders: a role for vitamin K. J Inherit Metab Dis 2018;41(2):249–55. doi: 10.1007/s10545-017-0113-8CrossRefGoogle ScholarPubMed
Rüether, K, et al. Adult Refsum disease: a form of tapetoretinal dystrophy accessible to therapy. Surv Ophthalmol 2010;55(6):531–8. doi: 10.1016/j.survophthal.2010.03.007Google Scholar
Baldwin, EJ, Gibberd, FB, Harley, C, Sidey, MC, Feher, MD, Wierzbicki, AS. The effectiveness of long-term dietary therapy in the treatment of adult Refsum disease. J Neurol Neurosurg Psychiatry 2010;81(9):954–7. doi: 10.1136/jnnp.2008.161059Google Scholar
Noguer, MT, Martinez, M. Visual follow-up in peroxisomal-disorder patients treated with docosahexaenoic acid ethyl ester. Invest Ophthalmol Vis Sci 2010;51(4): 2277–85. doi: 10.1167/iovs.09-4020Google Scholar
Paker, AM, et al. Docosahexaenoic acid therapy in peroxisomal diseases: results of a double-blind, randomized trial. Neurology 2010;75(9):826–30. doi: 10.1212/WNL.0b013e3181f07061Google Scholar
Bove, KE, Heubi, JE, Balistreri, WF, Setchell, KDR. Bile acid synthetic defects and liver disease: a comprehensive review. Pediatr Dev Pathol 2004;7(4):315–34. doi: 10.1007/s10024-002-1201-8Google Scholar
Klouwer, FCC, et al. The cholic acid extension study in Zellweger spectrum disorders: results and implications for therapy. J Inherit Metab Dis 2019;42(2):303–12. doi: 10.1002/jimd.12042Google Scholar
Berendse, K, et al. Cholic acid therapy in Zellweger spectrum disorders. J Inherit Metab Dis 2016;39(6):859–68. doi: 10.1007/s10545-016-9962-9Google Scholar
Heubi, JE, Bove, KE, Setchell, KDR. Oral cholic acid is efficacious and well tolerated in patients with bile acid synthesis and Zellweger spectrum disorders. J Pediatr Gastroenterol Nutr 2017;65(3):321–6. doi: 10.1097/MPG.0000000000001657Google Scholar
Klouwer, FCC, et al. Oral cholic acid in Zellweger spectrum disorders: a word of caution. J Pediatr Gastroenterol Nutr 2018;66(2):e57. doi: 10.1097/MPG.0000000000001763Google Scholar
Sokal, EM, et al. Hepatocyte transplantation in a 4-year-old girl with peroxisomal biogenesis disease: technique, safety, and metabolic follow-up1. Transplantation 2003;76(4):735–8. doi: 10.1097/01.TP.0000077420.81365.53Google Scholar
Van Maldergem, L, et al. Orthotopic liver transplantation from a living-related donor in an infant with a peroxisome biogenesis defect of the infantile Refsum disease type. J Inherit Metab Dis 2005;28(4):593600. doi: 10.1007/s10545-005-0593-9Google Scholar
Matsunami, M, et al. Living-donor liver transplantation from a heterozygous parent for infantile Refsum disease. Pediatrics 2016;137(6). doi: 10.1542/peds.2015-3102Google Scholar
Demaret, T, et al. Living-donor liver transplantation for mild Zellweger spectrum disorder: up to 17 years follow-up. Pediatr Transplant 2018;22(3):e13112. doi: 10.1111/petr.13112Google Scholar
Wang, RY, et al. Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study. J Inherit Metab Dis 2014;37(5):791–9. doi: 10.1007/s10545-014-9698-3Google Scholar
MacLean, GE, et al. Zellweger spectrum disorder patient-derived fibroblasts with the PEX1-Gly843Asp allele recover peroxisome functions in response to flavonoids. J Cell Biochem 2019;120(3):3243–58. doi: 10.1002/jcb.27591Google Scholar
Zhang, R, Chen, L, Jiralerspong, S, Snowden, A, Steinberg, S, Braverman, N. Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proc Natl Acad Sci USA 2010;107(12):5569–74. doi: 10.1073/pnas.0914960107Google Scholar
Berendse, K, Ebberink, MS, Ijlst, L, Poll, BT, Wanders, RJA, Waterham, HR. Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder. Orphanet J Rare Dis 2013;8:138. doi: 10.1186/1750-1172-8-138Google Scholar
Wei, H, Kemp, S, McGuinness, MC, Moser, AB, Smith, KD. Pharmacological induction of peroxisomes in peroxisome biogenesis disorders. Ann Neurol 2000;47(3):286–96.Google Scholar
Law, KB, et al. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders. Autophagy 2017;13(5):868–84. doi: 10.1080/15548627.2017.1291470Google Scholar
Wanders, RJA, Komen, J, Kemp, S. Fatty acid omega-oxidation as a rescue pathway for fatty acid oxidation disorders in humans. FEBS J 2011;278(2):182–94. doi: 10.1111/j.1742-4658.2010.07947.xGoogle Scholar
Brites, P, et al. Alkyl-glycerol rescues plasmalogen levels and pathology of ether-phospholipid deficient mice. PloS One 2011;6(12):e28539. doi: 10.1371/journal.pone.0028539Google Scholar
Braverman, N, et al. A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton. Mol Genet Metab 2010;99(4):408–16. doi: 10.1016/j.ymgme.2009.12.005Google Scholar
Fallatah, W, et al. Oral administration of a synthetic vinyl-ether plasmalogen normalizes open field activity in a mouse model of Rhizomelic chondrodysplasia punctata. Dis Model Mech Dec 2019. doi: 10.1242/dmm.042499Google Scholar

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