Peroxisomal Disorders

  • Nobuyuki ShimozawaEmail author


Peroxisomal disorders (PD) are genetic disorders caused by peroxisome dysfunction and are classified into two groups: genetic defects in peroxisome-localized proteins and genetic defects in peroxisomal biogenesis. The dawn of PD research came with the detailed analysis of the Zellweger syndrome, the prototype of PD. Even recently, new PD are still being identified by whole-exome sequencing analysis, which means that the concept of PD has been expanding. Furthermore, the role of peroxisome in cancer and age-related diseases has also been studied. In contrast, PD pathophysiology and treatment are not clarified yet completely and even in adrenoleukodystrophy, which is the most common PD, the prognosis of phenotype and disease in pre-symptomatic patients is a difficult task.

In this chapter, various types of PD based on patient clinical data will be described, which will be useful to researchers and clinicians. I hope that this chapter will be a valuable aid to many researchers and clinicians in a conjoint effort to overcome this intractable disease.


Peroxisome β-oxidation VLCFA Plasmalogens Phytanic acid Zellweger syndrome Adrenoleukodystrophy Whole-exome sequencing 



The author would like to thank Dr. Yasuyuki Suzuki for his guidance and collaboration at Gifu University, Dr. Ronald JA Wanders for his helpful comment, and Dr. A. Goto, Dr. K. Maeda, Dr. S. Matsui, Dr. K. Hibino, Dr. Y. Tanabe and Dr. R. Ikema for providing data of the patients, and further thank many patients and their parents for providing the resources.

The author memorializes the death of the late Professor Emeritus Takashi Hashimoto with deep grief. He was our great pioneer in the field of peroxisomal research, and has passed away on April 18th, 2019 at the age of 86. We would like to deeply grateful to him for his great contribution to the elucidation of peroxisomal disorders.

Ethics Statement

The diagnostic studies of PD are approved by the Ethical Committee of the Graduate School of Medicine, Gifu University.

Conflict of Interest

The author declares no conflict of interest.


  1. Abu-Safieh L, Alrashed M, Anazi S et al (2013) Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res 23:236–247PubMedPubMedCentralCrossRefGoogle Scholar
  2. Asare A, Levorse J, Fuchs E (2017) Coupling organelle inheritance with mitosis to balance growth and differentiation. Science 355:eaah4701PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bacino C, Chao YH, Seto E, Lotze T, Xia F, Jones RO, Moser A, Wangler MF (2015) A homozygous mutation in PEX16 identified by whole-exome sequencing ending a diagnostic odyssey. Mol Genet Metab Rep 5:15–18PubMedPubMedCentralCrossRefGoogle Scholar
  4. Bams-Mengerink AM, Majoie CB, Duran M, Wanders RJ, Van Hove J, Scheurer CD, Barth PG, Poll-The BT (2006) MRI of the brain and cervical spinal cord in rhizomelic chondrodysplasia punctate. Neurology 66:798–803PubMedCrossRefPubMedCentralGoogle Scholar
  5. Barøy T, Koster J, Strømme P et al (2015) A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform. Hum Mol Genet 24:5845–5854PubMedCrossRefPubMedCentralGoogle Scholar
  6. Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, Kass NE, Moser HW (2001) Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol 49:512–517PubMedCrossRefPubMedCentralGoogle Scholar
  7. Bjørgo K, Fjær R, Mørk HH, Ferdinandusse S, Falkenberg KD, Waterham HR, Øye AM, Sikiric A, Amundsen SS, Kulseth MA, Selmer K (2017) Biochemical and genetic characterization of an unusual mild PEX3-related Zellweger spectrum disorder. Mol Genet Metab 121:325–328PubMedCrossRefPubMedCentralGoogle Scholar
  8. Blomqvist M, Ahlberg K, Lindgren J, Ferdinandusse S, Asin-Cayuela J (2017) Identification of a novel mutation in PEX10 in a patient with attenuated Zellweger spectrum disorder: a case report. J Med Case Reports 11:218CrossRefGoogle Scholar
  9. Bowen P, Lee CSN, Zellweger H, Lindenberg R (1964) A familial syndrome of multiple congenital defects. Bull Johns Hopkins Hosp 114:402–414PubMedPubMedCentralGoogle Scholar
  10. Braverman N, Chen L, Lin P, Obie C, Steel G, Douglas P, Chakraborty PK, Clarke JTR, Boneh A, Moser A, Moser H, Valle D (2002) Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype. Hum Mutat 20:284–297PubMedCrossRefPubMedCentralGoogle Scholar
  11. Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, Steinberg SJ, Wangler MF, Rush ET, Hacia JG, Bose M (2016) Peroxisome biogenesis disorders in the Zellweger spectrum: an overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab 117:313–321PubMedCrossRefPubMedCentralGoogle Scholar
  12. van den Brink DM, Brites P, Haasjes J, Wierzbicki AS, Mitchell J, Lambert-Hamill M, de Belleroche J, Jansen GA, Waterham HR, Wanders RJA (2003) Identification of PEX7 as the second gene involved in Refsum disease. Am J Hum Genet 72:471–477PubMedPubMedCentralCrossRefGoogle Scholar
  13. Buchert R, Tawamie H, Smith C, Uebe S, Innes AM, Al Hallak B, Ekici AB, Sticht H, Schwarze B, Lamont RE, Parboosingh JS, Bernier FP, Abou Jamra R (2014) A peroxisomal disorder of severe intellectual disability, epilepsy, and cataracts due to fatty acyl-CoA reductase 1 deficiency. Am J Hum Genet 95:602–610PubMedPubMedCentralCrossRefGoogle Scholar
  14. Carlton VEH, Harris BZ, Puffenberg EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, Morton DH, Bull LN (2003) Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet 34:91–96PubMedCrossRefPubMedCentralGoogle Scholar
  15. Cipolla CM, Lodhi IJ (2017) Peroxisomal dysfunction in age-related diseases. Trends Endocrinol Metab 28:297–308PubMedPubMedCentralCrossRefGoogle Scholar
  16. Cuesta A, Pedrola L, Sevilla T, Garcia-Planells J, Chumillas MJ, Mayordomo F, LeGuern E, Marin I, Vilche JJ, Palau F (2002) The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat Genet 30:22–24PubMedCrossRefPubMedCentralGoogle Scholar
  17. Curiel J, Steinberg SJ, Bright S, Snowden A, Moser AB, Eichler F, Dubbs HA, Hacia JG, Ely JJ, Bezner J, Gean A, Vanderver A (2017) X-linked adrenoleukodystrophy in a chimpanzee due to an ABCD1 mutation reported in multiple unrelated humans. Mol Genet Metab 122:130–133PubMedCrossRefPubMedCentralGoogle Scholar
  18. Demaret T, Varma S, Stephenne X, Smets F, Scheers I, Wanders R, Van Maldergem L, Reding R, Sokal E (2018) Living-donor liver transplantation for mild Zellweger spectrum disorder: up to 17 years follow-up. Pediatr Transplant 22:e13112PubMedCrossRefPubMedCentralGoogle Scholar
  19. 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 47:608–615PubMedCrossRefPubMedCentralGoogle Scholar
  20. Ebberink MS, Koster J, Visser G, van Spronsen F, Stolte-Dijkstra I, Smit GP, Fock JM, Kemp S, Wanders RJ, Waterham HR (2012) A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11-beta gene. J Med Genet 49:307–313PubMedCrossRefPubMedCentralGoogle Scholar
  21. Eichler F, Duncan C, Musolino PL et al (2017) Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. N Engl J Med 377:1630–1638PubMedPubMedCentralCrossRefGoogle Scholar
  22. Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, Poll-The BT (2012) X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis 7:51PubMedPubMedCentralCrossRefGoogle Scholar
  23. Engelen M, Barbier M, Dijkstra IM, Schür R, de Bie RM, Verhamme C, Dijkgraaf MG, Aubourg PA, Wanders RJ, van Geel BM, de Visser M, Poll-The BT, Kemp S (2014) X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain 137:693–706PubMedCrossRefPubMedCentralGoogle Scholar
  24. Fabelo N, Martín V, Santpere G, Marín R, Torrent L, Ferrer I, Díaz M (2011) Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Med 17:1107–1118PubMedPubMedCentralCrossRefGoogle Scholar
  25. Falkenberg KD, Braverman NE, Moser AB et al (2017) Allelic expression imbalance promoting a mutant PEX6 allele causes Zellweger spectrum disorder. Am J Hum Genet 101:965–976PubMedPubMedCentralCrossRefGoogle Scholar
  26. Ferdinandusse S, Denis S, Clayton PT, Graham A, Rees JE, Allen JT, McLean BN, Brown AY, Vreken P, Waterham HR, Wanders RJ (2000) Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy. Nat Genet 24:188–191PubMedCrossRefPubMedCentralGoogle Scholar
  27. Ferdinandusse S, Kostopoulos P, Denis S, Rusch H, Overmars H, Dillmann U, Reith W, Haas D, Wanders RJ, Duran M, Marziniak M (2006) Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Am J Hum Genet 78:1046–1052PubMedPubMedCentralCrossRefGoogle Scholar
  28. Ferdinandusse S, Barker S, Lachlan K, Duran M, Waterham HR, Wanders RJ, Hammans S (2010) Adult peroxisomal acyl-coenzyme A oxidase deficiency with cerebellar and brainstem atrophy. J Neurol Neurosurg Psychiatry 81:310–312PubMedCrossRefPubMedCentralGoogle Scholar
  29. Ferdinandusse S, Jimenez-Sanchez G, Koster J et al (2015) A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum Mol Genet 24:361–370PubMedCrossRefPubMedCentralGoogle Scholar
  30. Ferdinandusse S, Falkenberg KD, Koster J, Mooyer PA, Jones R, van Roermund CWT, Pizzino A, Schrader M, Wanders RJA, Vanderver A, Waterham HR (2017) ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism. J Med Genet 54:330–337PubMedCrossRefPubMedCentralGoogle Scholar
  31. Frishberg Y, Zeharia A, Lyakhovetsky R, Bargal R, Belostotsky R (2014) Mutations in HAO1 encoding glycolate oxidase cause isolated glycolic aciduria. J Med Genet 51:526–529PubMedCrossRefPubMedCentralGoogle Scholar
  32. Fujino T, Yamada T, Asada T, Tsuboi Y, Wakana C, Mawatari S, Kono S (2017) Efficacy and blood plasmalogen changes by oral Administration Of Plasmalogen In Patients With Mild Alzheimer’s disease and mild cognitive impairment: a multicenter, randomized, double-blind, placebo-controlled trial. EBioMedicine 17:199–205PubMedPubMedCentralCrossRefGoogle Scholar
  33. Funato M, Shimozawa N, Nagase T, Takemoto Y, Suzuki Y, Imamura Y, Matsumoto T, Tsukamoto T, Kojidani T, Osumi T, Fukao T, Kondo N (2006) Aberrant peroxisome morphology in peroxisomal beta-oxidation enzyme deficiencies. Brain Dev 28:287–292PubMedCrossRefPubMedCentralGoogle Scholar
  34. van Geel BM, Poll-The BT, Verrips A, Boelens JJ, Kemp S, Engelen M (2015) Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis 38:359–361PubMedCrossRefPubMedCentralGoogle Scholar
  35. Gerber S, Charif M, Chevrollier A et al (2017) Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission. Brain 140:2586–2596PubMedCrossRefPubMedCentralGoogle Scholar
  36. Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisniewski HK, Ritch RH, Norton WT, Rapin I, Gartner LM (1973) Peroxisomal and mitochondrial defects in the cerebro-hepatorenal syndrome. Science 182:62–64PubMedCrossRefGoogle Scholar
  37. Han X, Holtzman DM, McKeel DW Jr (2001) Plasmalogen deficiency in early Alzheimer’s disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry. J Neurochem 77:1168–1180PubMedCrossRefGoogle Scholar
  38. Huber N, Guimaraes S, Schrader M, Suter U, Niemann A (2013) Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission. EMBO Rep 14:545–552PubMedPubMedCentralCrossRefGoogle Scholar
  39. Huffnagel IC, Laheji FK, Aziz-Bose R, Tritos NA, Marino R, Linthorst GE, Kemp S, Engelen M, Eichler F (2019) The natural history of adrenal insufficiency in X-linked adrenoleukodystrophy: an international collaboration. J Clin Endocrinol Metab 104:118–126PubMedCrossRefGoogle Scholar
  40. Huybrechts SJ, Van Veldhoven PP, Brees C, Mannaerts GP, Los GV, Fransen M (2009) Peroxisome dynamics in cultured mammalian cells. Traffic 10:1722–1733PubMedCrossRefGoogle Scholar
  41. Islinger M, Voelkl A, Fahimi HD, Schrader M (2018) The peroxisome: an update on mysteries 2.0. Histochem Cell Biol 150:443–471PubMedPubMedCentralCrossRefGoogle Scholar
  42. Kallijärvi J, Avela K, Lipsanen-Nyman M, Ulmanen I, Lehesjoki AE (2002) The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of Mulibrey Nanism as a new peroxisomal disorder. Am J Hum Genet 70:1215–1228PubMedPubMedCentralCrossRefGoogle Scholar
  43. Kato K, Maemura R, Wakamatsu M et al (2018) Allogeneic stem cell transplantation with reduced intensity conditioning for patients with adrenoleukodystrophy. Mol Genet Metab Rep 18:1–6PubMedPubMedCentralGoogle Scholar
  44. Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, Cutting GR, Wanders RJ, Moser HW (2001) ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat 18:499–515PubMedCrossRefPubMedCentralGoogle Scholar
  45. Khan M, Singh J, Singh I (2008) Plasmalogen deficiency in cerebral adrenoleukodystrophy and its modulation by lovastatin. J Neurochem 106:1766–1779PubMedPubMedCentralGoogle Scholar
  46. Kühl JS, Suarez F, Gillett GT, Hemmati PG, Snowden JA, Stadler M, Vuong GL, Aubourg P, Köhler W, Arnold R (2017) Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy. Brain 140:953–966PubMedCrossRefPubMedCentralGoogle Scholar
  47. Kumar KR, Wali GM, Kamate M, Wali G, Minoche AE, Puttick C, Pinese M, Gayevskiy V, Dinger ME, Roscioli T, Sue CM, Cowley MJ (2016) Defining the genetic basis of early onset hereditary spastic paraplegia using whole genome sequencing. Neurogenetics 17:265–270PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lazarow PB, De Duve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci U S A 73:2043–2046PubMedPubMedCentralCrossRefGoogle Scholar
  49. Legakis JE, Koepke JI, Jedeszko C, Barlaskar F, Terlecky LJ, Edwards HJ, Walton PA, Terlecky SR (2002) Peroxisome senescence in human fibroblasts. Mol Biol Cell 13:4243–4255PubMedPubMedCentralCrossRefGoogle Scholar
  50. López-Erauskin J, Fourcade S, Galino J, Ruiz M, Schlüter A, Naudi A, Jove M, Portero-Otin M, Pamplona R, Ferrer I, Pujol A (2011) Antioxidants halt axonal degeneration in a mouse model of X-adrenoleukodystrophy. Ann Neurol 70:84–92PubMedPubMedCentralCrossRefGoogle Scholar
  51. Matsui S, Funahashi M, Honda A, Shimozawa N (2013) Newly identified milder phenotype of peroxisome biogenesis disorder caused by mutated PEX3 gene. Brain Dev 35:842–848PubMedCrossRefPubMedCentralGoogle Scholar
  52. Matsunami M, Shimozawa N, Fukuda A, Kumagai T, Kubota M, Chong PF, Kasahara M (2016) Living-donor liver transplantation from a heterozygous parent for infantile Refsum disease. Pediatrics 137:e20153102PubMedCrossRefPubMedCentralGoogle Scholar
  53. McMillan HJ, Worthylake T, Schwartzentruber J et al (2012) Specific combination of compound heterozygous mutations in 17beta-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. Orphanet J Rare Dis 7:1–9CrossRefGoogle Scholar
  54. Mignarri A, Vinciguerra C, Giorgio A, Ferdinandusse S, Waterham H, Wanders R, Bertini E, Dotti MT, Federico A (2012) Zellweger spectrum disorder with mild phenotype caused by PEX2 gene mutations. JIMD Rep 6:43–46PubMedPubMedCentralCrossRefGoogle Scholar
  55. Nagy T, Paszti E, Kaplar M, Bhattoa HP, Goth L (2015) Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia. Mutat Res 772:10–14PubMedCrossRefPubMedCentralGoogle Scholar
  56. Ohba C, Osaka H, Iai M (2013) Diagnostic utility of whole exome sequencing in patients showing cerebellar and/or vermis atrophy in childhood. Neurogenetics 14:225–232PubMedCrossRefPubMedCentralGoogle Scholar
  57. Peters C, Charnas LR, Tan Y et al (2004) Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood 104:881–888PubMedCrossRefPubMedCentralGoogle Scholar
  58. Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King MC (2010) Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet 87:282–288PubMedPubMedCentralCrossRefGoogle Scholar
  59. Pujol A, Hindelang C, Callizot N, Bartsch U, Schachner M, Mandel JL (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum Mol Genet 11:499–505PubMedCrossRefPubMedCentralGoogle Scholar
  60. Raas-Rothschild A, Wanders RJ, Mooijer PA, Gootjes J, Waterham HR, Gutman A, Suzuki Y, Shimozawa N, Kondo N, Eshel G, Espeel M, Roels F, Korman SH (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 70:1062–1068PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ratbi I, Falkenberg KD, Sommen M et al (2015) Heimler syndrome is caused by hypomorphic mutations in the peroxisome-biogenesis genes PEX1 and PEX6. Am J Hum Genet 97:535–545PubMedPubMedCentralCrossRefGoogle Scholar
  62. Raymond GV, Aubourg P, Paker A et al (2018) Survival and functional outcomes in boys with cerebral adrenoleukodystrophy with and without hematopoietic stem cell transplantation. Biol Blood Marrow Transplant S1083-8791:30603–30607Google Scholar
  63. Régal L, Ebberink MS, Goemans N, Wanders RJ, De Meirleir L, Jaeken J, Schrooten M, Van Coster R, Waterham HR (2010) Mutations in PEX10 are a cause of autosomal recessive ataxia. Ann Neurol 68:259–263PubMedPubMedCentralGoogle Scholar
  64. Renaud M, Guissart C, Mallaret M, Ferdinandusse S, Cheillan D, Drouot N, Muller J, Claustres M, Tranchant C, Anheim M, Koenig M (2016) Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia. J Neurol 263:1552–1558PubMedCrossRefPubMedCentralGoogle Scholar
  65. Sá MJ, Rocha JC, Almeida MF, Carmona C, Martins E, Miranda V, Coutinho M, Ferreira R, Pacheco S, Laranjeira F, Ribeiro I, Fortuna AM, Lacerda L (2016) Infantile Refsum Disease: influence of dietary treatment on plasma phytanic acid levels. JIMD Rep 26:53–60PubMedCrossRefPubMedCentralGoogle Scholar
  66. Schabhüttl M, Wieland T, Senderek J, Baets J, Timmerman V, De Jonghe P, Reilly MM, Stieglbauer K, Laich E, Windhager R, Erwa W, Trajanoski S, Strom TM, Auer-Grumbach M (2014) Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges. J Neurol 261:970–982PubMedCrossRefPubMedCentralGoogle Scholar
  67. Setchell KD, Heubi JE, Bove KE, O’Connell NC, Brewsaug T, Steinberg SJ, Moser A, Squires RH Jr (2003) Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy. Gastroenterology 124:217–232PubMedCrossRefPubMedCentralGoogle Scholar
  68. Sevin C, Ferdinandusse S, Waterham H, Wanders RJ, Aubourg P (2011) Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene. Orphanet J Rare Dis 6:8PubMedPubMedCentralCrossRefGoogle Scholar
  69. Shimozawa N (2011) Molecular and clinical findings and diagnostic flowchart of peroxisomal diseases. Brain Dev 33:770–776PubMedCrossRefPubMedCentralGoogle Scholar
  70. Shimozawa N, Tsukamoto T, Suzuki Y, Orii T, Shirayoshi Y, Mori T, Fujiki Y (1992) A human gene responsible for Zellweger syndrome that affects peroxisome assembly. Science 255:1132–1134PubMedCrossRefPubMedCentralGoogle Scholar
  71. Shimozawa N, Tsukamoto T, Nagase T, Takemoto Y, Koyama N, Suzuki Y, Komori M, Osumi T, Jeannette G, Wanders RJ, Kondo N (2004) Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene. Hum Mutat 23:552–558PubMedCrossRefPubMedCentralGoogle Scholar
  72. Smith CE, Poulter JA, Levin AV, Capasso JE, Price S, Ben-Yosef T, Sharony R, Newman WG, Shore RC, Brookes SJ, Mighell AJ, Inglehearn CF (2016) Spectrum of PEX1 and PEX6 variants in Heimler syndrome. Eur J Hum Genet 24:1565–1571PubMedPubMedCentralCrossRefGoogle Scholar
  73. Stancill JS, Broniowska KA, Oleson BJ, Naatz A, Corbett JA (2019) Pancreatic β-cells detoxify H2O2 through the peroxiredoxin/thioredoxin antioxidant system. J Biol Chem 294:4843PubMedCrossRefPubMedCentralGoogle Scholar
  74. Takahara S, Miyamoto H (1948) Three cases of progressive oral gangrene due to lack of catalase in the blood. Nippon Jibiinkoka Gakkai Kaiho 51:163Google Scholar
  75. Teigler A, Komljenovic D, Draguhn A, Gorgas K, Just WW (2009) Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum. Hum Mol Genet 18:1897–1908PubMedPubMedCentralCrossRefGoogle Scholar
  76. Tran C, Hewson S, Steinberg SJ, Mercimek-Mahmutoglu S (2014) Late-onset Zellweger spectrum disorder caused by PEX6 mutations mimicking X-linked adrenoleukodystrophy. Pediatr Neurol 51:262–265PubMedCrossRefGoogle Scholar
  77. Uyama T, Kawai K, Kono N, Watanabe M, Tsuboi K, Inoue T, Araki N, Arai H, Ueda N (2015) Interaction of phospholipase A/acyltransferase-3 with Pex19p: a possible involvement in the down-regulation of peroxisomes. J Biol Chem 290:17520–17534PubMedPubMedCentralCrossRefGoogle Scholar
  78. Ventura MJ, Wheaton D, Xu M, Birch D, Bowne SJ, Sullivan LS, Daiger SP, Whitney AE, Jones RO, Moser AB, Chen R, Wangler MF (2016) Diagnosis of a mild peroxisomal phenotype with next-generation sequencing. Mol Genet Metab Rep 9:75–78PubMedPubMedCentralCrossRefGoogle Scholar
  79. Vilarinho S, Sari S, Mazzacuva F, Bilgüvar K, Esendagli-Yilmaz G, Jain D, Akyol G, Dalgiç B, Günel M, Clayton PT, Lifton RP (2016) ACOX2 deficiency: a disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment. Proc Natl Acad Sci U S A 113:11289–11293PubMedPubMedCentralCrossRefGoogle Scholar
  80. Wanders RJ, Poll-The BT (2017) Role of peroxisomes in human lipid metabolism and its importance for neurological development. Neurosci Lett 637:11–17PubMedCrossRefPubMedCentralGoogle Scholar
  81. Wang Y, Busin R, Reeves C et al (2011) X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Mol Genet Metab 104:160–166PubMedCrossRefGoogle Scholar
  82. Wang S, Horn PJ, Liou LC, Muggeridge MI, Zhang Z, Chapman KD, Witt SN (2013) A peroxisome biogenesis deficiency prevents the binding of alpha-synuclein to lipid droplets in lipid-loaded yeast. Biochem Biophys Res Commun 438:452–456PubMedPubMedCentralCrossRefGoogle Scholar
  83. Wang RY, Monuki ES, Powers J, Schwartz PH, Watkins PA, Shi Y, Moser A, Shrier DA, Waterham HR, Nugent DJ, Abdenur JE (2014) Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study. J Inherit Metab Dis 37:791–799PubMedPubMedCentralCrossRefGoogle Scholar
  84. Wang W, Xia ZJ, Farré JC, Subramani S (2017) TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import. J Cell Biol 216:2843–2858PubMedPubMedCentralCrossRefGoogle Scholar
  85. Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356:1736–1741PubMedCrossRefPubMedCentralGoogle Scholar
  86. Yakunin E, Moser A, Loeb V, Saada A, Faust P, Crane DI, Baes M, Sharon R (2010) Alpha-Synuclein abnormalities in mouse models of peroxisome biogenesis disorders. J Neurosci Res 88:866–876PubMedPubMedCentralGoogle Scholar
  87. Yamashita T, Mitsui J, Shimozawa N et al (2017) Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype. J Neurol Sci 375:424–429PubMedCrossRefPubMedCentralGoogle Scholar
  88. Yoon G, Malam Z, Paton T, Marshall CR, Hyatt E, Ivakine Z, Scherer SW, Lee K-S, Hawkins C, Cohn RD (2016) Lethal disorder of mitochondrial fission caused by mutations in DNM1. J Pediatr 171:313–316PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Division of Genomics Research, Life Science Research CenterGifu UniversityGifuJapan
  2. 2.Department of PediatricsGifu University School of MedicineGifuJapan

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