Mutations in the gene encoding peroxisomal α-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy

Ferdinandusse, Sacha; Denis, Simone; Clayton, Peter T.; Graham, Andrew; Rees, John E.; Allen, John T.; McLean, Brendan N.; Brown, Ann Y.; Vreken, Peter; Waterham, Hans R.; Wanders, Ronald J.A.

doi:10.1038/72861

Cited by 263Hereditary Neurological DisordersMetabolism and Genetic DisordersNeurological diseases and metabolism

Mutations in the gene encoding peroxisomal α-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy

Ferdinandusse, Sacha, Denis, Simone, Clayton, Peter T., Graham, Andrew, Rees, John E., Allen, John T., McLean, Brendan N., Brown, Ann Y. +3 more·2000·Nature Genetics

DOI 10.1038/72861

Open this paper in CoChat — free account

Abstract

Sensory motor neuropathy is associated with various inherited disorders including Charcot-Marie-Tooth disease, X-linked adrenoleukodystrophy/adrenomyeloneuropathy and Refsum disease. In the latter two, the neuropathy is thought to result from the accumulation of specific fatty acids. We describe here three patients with elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates. Two of the patients suffered from adult-onset sensory motor neuropathy. One patient also had pigmentary retinopathy, suggesting Refsum disease, whereas the other patient had upper motor neuron signs in the legs, suggesting adrenomyeloneuropathy. The third patient was a child without neuropathy. In all three patients we discovered a deficiency of alpha-methylacyl-CoA racemase (AMACR). This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers, which are the only stereoisomers that can be degraded via peroxisomal beta-oxidation. Sequence analysis of AMACR cDNA from the patients identified two different mutations that are likely to cause disease, based on analysis in Escherichia coli. Our findings have implications for the diagnosis of adult-onset neuropathies of unknown aetiology.

Integrity signals

Registry

Crossref · 10.1038/72861

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Pristanic acid and the bile acid intermediates DHCA and THCA, but not VLCFA, accumulate in AMACR-deficient patients.
“Accordingly, pristanic acid and the bile acid intermediates DHCA and THCA, but not VLCFA, accumulate in AMACR-deficient patients (Fig. 1) [93].”
From Peroxisomes in brain development and function (2016) · cites this paper as [93]

Refsum disease is caused by mutations in the phytanoyl–CoA hydroxylase gene
Jansen, G. A., Oftnan, R., Ferdinandusse, S., IJlst, L., Muijsers, A. O., Skjeldal, O. H., Stokke, O., Jakobs, C., BESLEY, G. T. N., Wraith, J. E., et al. (1997) · Nature Genetics · doi:10.1038/ng1097-190 · Cited by 306 · see citing works
Identification of PAHX, a Refsum disease gene
Mihalik, S. J., Morrell, J. C., Kim, D., Sacksteder, K. A., Watkins, P. A., & Gould, S. J. (1997) · Nature Genetics · doi:10.1038/ng1097-185 · Cited by 244 · see citing works
Comparison of the binding affinities of acyl-CoA-binding protein and fatty-acid-binding protein for long-chain acyl-CoA esters
Rasmussen, J. T., Börchers, T., & Knudsen, J. (1990) · Biochemical Journal · doi:10.1042/bj2650849 · Cited by 195 · see citing works
Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the α-subunit of the mitochondrial trifunctional protein
IJlst, L., Wanders, R. J. A., Ushikubo, S., Kamijo, T., & Hashimoto, T. (1994) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(94)90064-7 · Cited by 158 · see citing works
Purification and Characterization of an alpha-Methylacyl-CoA Racemase from Human Liver
Schmitz, W., Albers, C., Fingerhut, R., & Conzelmann, E. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20766.x · Cited by 124 · see citing works
The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder
Dubois-Dalcq, M., Feigenbaum, V., & Aubourg, P. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01319-8 · Cited by 121 · see citing works
Purification and properties of an α‐methylacyl‐CoA racemase from rat liver
Schmitz, W., Fingerhut, R., & Conzelmann, E. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb18870.x · Cited by 116 · see citing works
Rapid stable isotope dilution analysis of very-long-chain fatty acids, pristanic acid and phytanic acid using gas chromatography–electron impact mass spectrometry
Vreken, P., van Lint, A. E. M., Bootsma, A. H., Overmars, H., Wanders, R. J. A., & Gennip, A. H. (1998) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00186-8 · Cited by 99 · see citing works
Measurement of peroxisomal fatty acid β‐oxidation in cultured human skin fibroblasts
Wanders, R. J. A., Denis, S. W., Ruiter, J. P. N., Schutgens, R. B. H., van Roermund, C. W. T., & Jacobs, B. S. (1995) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711434 · Cited by 95 · see citing works
Plasma and Red Blood Cell Fatty Acids in Peroxisomal Disorders
Moser, A. B., Jones, D. S., Raymond, G. V., & Moser, H. W. (1999) · Neurochemical Research · doi:10.1023/a:1022549618333 · Cited by 93 · see citing works
Charcot-Marie-Tooth Disease and Related Inherited Neuropathies
Murakami, T., Garcia, C. A., Reiter, L. T., & Lupski, J. R. (1996) · Medicine · doi:10.1097/00005792-199609000-00001 · Cited by 86 · see citing works
Hereditary Peripheral Neuropathies: Clinical Forms, Genetics, and Molecular Mechanisms
Warner, L. E., García, C., & Lupski, J. R. (1999) · Annual Review of Medicine · doi:10.1146/annurev.med.50.1.263 · Cited by 85 · see citing works
The occurrence of diastereomers of phytanic and pristanic acids and their determination by gas‐liquid chromatography
ACKMAN, R. G., & Hansen, R. (1967) · Lipids · doi:10.1007/bf02531848 · Cited by 82 · see citing works
Peroxisomal β‐oxidation of 2‐methyl‐branched acyl‐CoA esters stereospecific recognition of the 2S‐methyl compounds by trihydroxycoprostanoyl‐CoA oxidase and pristanoyl‐CoA oxidase
Veldhoven, P. P. V., Croes, K., Asselberghs, S., Herdewijn, P. A., & Mannaerts, G. P. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00508-x · Cited by 75 · see citing works
Refsum’s Disease: Management by Diet and Plasmapheresis
Jp, H., Meier, C. F., Rousselle, L., Quadri, P., & Bogousslavsky, J. (2008) · European Neurology · doi:10.1159/000115788 · Cited by 63 · see citing works
Substrate Stereospecificity in Oxidation of (25S)-3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA by Peroxisomal Trihydroxy-5β- cholestanoyl-CoA Oxidase
Pedersen, J. I., Veggan, T., & Björkhem, I. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0981 · Cited by 35 · see citing works
Bile acids in peroxisomal disorders
Eldere, J. V., Parmentier, G. G., Eyssen, H., Wanders, R. J. A., Schutgens, R. B. H., Vamecq, J., Hoof, F. V., Poll‐The, B. T., & Saudubray, J. (1987) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1987.tb01131.x · Cited by 33 · see citing works
2-Methylacyl racemase: a coupled assay based on the use of pristanoyl-CoA oxidase/peroxidase and reinvestigation of its subcellular distribution in rat and human liver
Veldhoven, P. P. V., Croes, K., Casteels, M., & Mannaerts, G. P. (1997) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/s0005-2760(97)00053-2 · Cited by 31 · see citing works
Stereochemistry of the α-oxidation of 3-methyl-branched fatty acids in rat liver
Croes, K., Casteels, M., Dieuaide‐Noubhani, M., Mannaerts, G. P., & Veldhoven, P. P. V. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32139-8 · Cited by 30 · see citing works
Molecular cloning of cDNA species for rat and mouse liver α-methylacyl-CoA racemases
Schmitz, W., Helander, H. M., Hiltunen, J. K., & Conzelmann, E. (1997) · Biochemical Journal · doi:10.1042/bj3260883 · Cited by 30 · see citing works
Configuration at C-25 in 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestan-26-oic acid isolated from human bile
Batta, A. K., Salen, G., Shefer, S., Dayal, B., & Tint, G. S. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38028-7 · Cited by 22 · see citing works
Niemann–Pick disease type C and defective peroxisomal β‐oxidation of branched‐chain substrates
Sequeira, J. S. S., Vellodi, A., Vanier, M. T., & Clayton, P. T. (1998) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1005395709826 · Cited by 12 · see citing works
Substrate specificity of THCA-CoA oxidases from rat liver light mitochondrial fractions on dehydrogenation of 3α,7α,12α-trihydroxy-5β-cholestanoic acid CoA thioester
Ikegawa, S., Goto, T., Mano, N., & Goto, J. (1998) · Steroids · doi:10.1016/s0039-128x(98)00070-1 · Cited by 8 · see citing works

Flagged first, then by citations

Sorted by citations

The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069 · see citing works
Biochemistry of mammalian peroxisomes revisited
Wanders, R. J. A., & Waterham, H. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133329 · Cited by 995 · see citing works
Self-citation
Bile acids: Chemistry, physiology, and pathophysiology
Monte, M. J., Marı́n, J. J. G., Antelo, Á., & Tato, J. V. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.804 · Cited by 569 · see citing works
Peroxisomal β-oxidation—A metabolic pathway with multiple functions
Poirier, Y., Antonenkov, V. D., Glumoff, T., & Hiltunen, J. K. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.08.034 · Cited by 497 · see citing works
Human disorders of peroxisome metabolism and biogenesis
Waterham, H. R., Ferdinandusse, S., & Wanders, R. J. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.11.015 · Cited by 368 · see citing works
Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism
Veldhoven, P. P. V. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r005959 · Cited by 328 · see citing works
Alpha-Methylacyl-CoA Racemase
Zhou, M., Chinnaiyan, A. M., Kleer, C. G., Lucas, P. C., & Rubin, M. A. (2002) · The American Journal of Surgical Pathology · doi:10.1097/00000478-200207000-00012 · Cited by 296 · see citing works
SPTLC1 is mutated in hereditary sensory neuropathy, type 1
Bejaoui, K., Wu, C., Scheffler, M. D., Haan, G., Ashby, P., Wu, L., de Jong, P., & Brown, R. H. (2001) · Nature Genetics · doi:10.1038/85817 · Cited by 292 · see citing works
The peroxisome: an update on mysteries 2.0
Islinger, M., Völkl, A., Fahimi, H. D., & Schrader, M. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1722-5 · Cited by 287 · see citing works
Peroxisomal disorders: The single peroxisomal enzyme deficiencies
Wanders, R. J. A., & Waterham, H. R. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.08.010 · Cited by 279 · see citing works
Decrease and Gain of Gene Expression Are Equally Discriminatory Markers for Prostate Carcinoma
Ernst, T., Hergenhahn, M., Kenzelmann, M., Cohen, C. D., Bonrouhi, M., Weninger, A., Klären, R., Gröne, E. F., Wiesel, M., Güdemann, C., et al. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61165-0 · Cited by 258 · see citing works
Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka
Fukamachi, S., Shimada, A., & Shima, A. (2001) · Nature Genetics · doi:10.1038/ng584 · Cited by 245 · see citing works
Metabolic functions of peroxisomes in health and disease
Wanders, R. J. A. (2013) · Biochimie · doi:10.1016/j.biochi.2013.08.022 · Cited by 232 · see citing works
Fatty acid omega‐oxidation as a rescue pathway for fatty acid oxidation disorders in humans
Wanders, R. J. A., Komen, J. C., & Kemp, S. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07947.x · Cited by 221 · see citing works
Peroxisomes, lipid metabolism, and peroxisomal disorders
Wanders, R. J. A. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.08.016 · Cited by 205 · see citing works
Evolution and diversity of copy number variation in the great ape lineagePreprint
Sudmant, P. H., Huddleston, J., Catacchio, C. R., Malig, M., Hillier, L. W., Baker, C. A., Mohajeri, K., Kondova, I. I., Bontrop, R. E., Persengiev, S. P., et al. (2013) · Genome Research · doi:10.1101/gr.158543.113 · Cited by 195 · see citing works
Peroxisomes in brain development and function
Berger, J., Dorninger, F., Forss-Petter, S., & Kunze, M. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.12.005 · Cited by 194 · see citing works
Pathological and molecular mechanisms of prostate carcinogenesis: Implications for diagnosis, detection, prevention, and treatment
Marzo, A. M. D., DeWeese, T. L., Platz, E. A., Meeker, A. K., Nakayama, M., Epstein, J. I., Isaacs, W. B., & Nelson, W. G. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10747 · Cited by 191 · see citing works
Refsum's disease: a peroxisomal disorder affecting phytanic acid α‐oxidation
Wierzbicki, A. S., Lloyd, M. D., Schofield, C. J., Feher, M. D., & Gibberd, F. B. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00766.x · Cited by 190 · see citing works
Subcellular localization and physiological role of α-methylacyl-CoA racemase
Ferdinandusse, S., Denis, S. W., IJlst, L., Dacremont, G., Waterham, H. R., & Wanders, R. J. A. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31983-0 · Cited by 183 · see citing works
MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing
Haugarvoll, K., Johansson, S., Tzoulis, C., Haukanes, B. I., Bredrup, C., Neckelmann, G., Boman, H., Knappskog, P. M., & Bindoff, L. A. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-1 · Cited by 181 · see citing works
Liver disease caused by failure to racemize trihydroxycholestanoic acid: Gene mutation and effect of bile acid therapy
Setchell, K. D. R., Heubi, J. E., Bove, K. E., O’Connell, N. C., Brewsaugh, T., Steinberg, S. J., Moser, A. B., & Squires, R. H. (2003) · Gastroenterology · doi:10.1053/gast.2003.50017 · Cited by 175 · see citing works
Metabolic and molecular basis of peroxisomal disorders: A review
Wanders, R. J. A. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20661 · Cited by 170 · see citing works
Peroxisomal branched chain fatty acid ?-oxidation pathway is upregulated in prostate cancer
Zha, S., Ferdinandusse, S., Hicks, J. L., Denis, S. W., Dunn, T. A., Wanders, R. J. A., Luo, J., Marzo, A. M. D., & Isaacs, W. B. (2004) · The Prostate · doi:10.1002/pros.20177 · Cited by 164 · see citing works
Bile acid analysis in human disorders of bile acid biosynthesis
Vaz, F. M., & Ferdinandusse, S. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.03.003 · Cited by 155 · see citing works
Bile Acid Synthetic Defects and Liver Disease: A Comprehensive Review
Bove, K. E., Heubi, J. E., Balistreri, W. F., & Setchell, K. D. R. (2002) · Pediatric and Developmental Pathology · doi:10.1007/s10024-002-1201-8 · Cited by 152 · see citing works
Peroxisomes, lipid metabolism and lipotoxicity
Wanders, R. J. A., Ferdinandusse, S., Brites, P., & Kemp, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.01.001 · Cited by 169 · see citing works
Mechanisms of disease: inborn errors of bile acid synthesis
Sundaram, S. S., Bove, K. E., Lovell, M. A., & Sokol, R. J. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1179 · Cited by 146 · see citing works
Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy
Ferdinandusse, S., Kostopoulos, P., Denis, S., Rusch, H., Overmars, H., Dillmann, U., Reith, W., Haas, D., Wanders, R. J. A., Duran, M., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/503921 · Cited by 145 · see citing works
Alpha-methylacyl-CoA racemase as an androgen-independent growth modifier in prostate cancer.
Zha, S., Ferdinandusse, S., Denis, S. W., Wanders, R. J. A., Ewing, C. M., Luo, J., Marzo, A. M. D., & Isaacs, W. B. (2003) · PubMed · Cited by 141 · see citing works
AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease
Dorer, R. K., & Odze, R. D. (2006) · The American Journal of Surgical Pathology · doi:10.1097/01.pas.0000213268.30468.b4 · Cited by 137 · see citing works
THE GENETICS OF PEROXISOME BIOGENESIS
Sacksteder, K. A., & Gould, S. J. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.623 · Cited by 130 · see citing works
Mutations in the sterol 27‐hydoxylase gene (CYP27A) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis
Clayton, P. T., Verrips, A., Sistermans, E. A., Mann, A., Mieli‐Vergani, G., & Wevers, R. A. (2002) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1021211520034 · Cited by 123 · see citing works
Peroxisome biogenesis disorders
Argyriou, C., D’Agostino, D., & Braverman, N. (2016) · Translational Science of Rare Diseases · doi:10.3233/trd-160003 · Cited by 126 · see citing works
α‐Methylacyl‐CoA racemase – an ‘obscure’ metabolic enzyme takes centre stage
Lloyd, M. D., Darley, D. J., Wierzbicki, A. S., & Threadgill, M. D. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06290.x · Cited by 114 · see citing works
Peroxisomes and bile acid biosynthesis
Ferdinandusse, S., & Houten, S. M. (2006) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2006.09.001 · Cited by 108 · see citing works
Refsum Disease, Peroxisomes and Phytanic Acid Oxidation: A Review
Wanders, R. J. A., Jansen, G. A., & Skjeldal, O. H. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.11.1021 · Cited by 106 · see citing works
A role for the human peroxisomal half-transporter ABCD3 in the oxidation of dicarboxylic acids
van Roermund, C. W. T., IJlst, L., Wagemans, T., Wanders, R. J. A., & Waterham, H. R. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.12.001 · Cited by 101 · see citing works
Oxysterols as lipid mediators: Their biosynthetic genes, enzymes and metabolites
Griffiths, W. J., & Wang, Y. (2019) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2019.106381 · Cited by 102 · see citing works
α-Methylacyl-CoA racemase (AMACR): Metabolic enzyme, drug metabolizer and cancer marker P504S
Lloyd, M. D., Yevglevskis, M., Lee, G. L., Wood, P. J., Threadgill, M. D., & Woodman, T. J. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2013.01.001 · Cited by 96 · see citing works
Human metabolism of phytanic acid and pristanic acid
Verhoeven‐Duif, N. M., & Jakobs, C. (2001) · Progress in Lipid Research · doi:10.1016/s0163-7827(01)00011-x · Cited by 94 · see citing works
ACOX2 deficiency: A disorder of bile acid synthesis with transaminase elevation, liver fibrosis, ataxia, and cognitive impairment
Vilarinho, S., Sarı, S., Mazzacuva, F., Bilgüvar, K., Esendağlı‐Yılmaz, G., Jain, D., Akyol, G., Dalgıç, B., Günel, M., Clayton, P. T., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613228113 · Cited by 96 · see citing works
Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders
Poll-The, B. T., & Gärtner, J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.03.011 · Cited by 85 · see citing works
α-Methylacyl CoA racemase (P504S): overview and potential uses in diagnostic pathology as applied to prostate needle biopsies
Evans, A. J. (2003) · Journal of Clinical Pathology · doi:10.1136/jcp.56.12.892 · Cited by 86 · see citing works
A mouse model for α-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids
Savolainen, K., Kotti, T. J., Schmitz, W., Savolainen, T. I., Sormunen, R. T., Ilves, M., Vainio, S. J., Conzelmann, E., & Hiltunen, J. K. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh107 · Cited by 83 · see citing works
Inborn Errors of Bile Acid Metabolism
Heubi, J. E., Setchell, K. D. R., & Bove, K. E. (2018) · Clinics in Liver Disease · doi:10.1016/j.cld.2018.06.006 · Cited by 82 · see citing works
Elevated α-Methylacyl-CoA Racemase Enzymatic Activity in Prostate Cancer
Kumar‐Sinha, C., Shah, R. B., Laxman, B., Tomlins, S. A., Harwood, J., Schmitz, W., Conzelmann, E., Sanda, M. G., Wei, J. T., Rubin, M. A., et al. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63167-7 · Cited by 79 · see citing works
The chemical biology of branched-chain lipid metabolism
Mukherji, M., Schofield, C. J., Wierzbicki, A. S., Jansen, G. A., Wanders, R. J. A., & Lloyd, M. D. (2003) · Progress in Lipid Research · doi:10.1016/s0163-7827(03)00016-x · Cited by 77 · see citing works
Peripheral neuropathy in complex inherited diseases: an approach to diagnosis
Rossor, A. M., Carr, A. S., Devine, H. E., Hoskote, C., Pelayo‐Negro, A. L., Pareyson, D., Shy, M. E., Scherer, S. S., & Reilly, M. M. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-313960 · Cited by 77 · see citing works
Refsum's disease
Wills, A. J. (2001) · QJM · doi:10.1093/qjmed/94.8.403 · Cited by 76 · see citing works
Peroxisomal disorders
Aubourg, P. R., & Wanders, R. J. A. (2013) · Handbook of clinical neurology · doi:10.1016/b978-0-444-59565-2.00028-9 · Cited by 75 · see citing works
Genetics of familial intrahepatic cholestasis syndromes
van Mil, S. W. C., Houwen, R. H. J., & Klomp, L. W. J. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2004.026187 · Cited by 69 · see citing works
Peroxisomal disorders affecting phytanic acid α-oxidation: a review
Wierzbicki, A. S. (2007) · Biochemical Society Transactions · doi:10.1042/bst0350881 · Cited by 69 · see citing works
Inherited ichthyosis: Syndromic forms
Yoneda, K. (2016) · The Journal of Dermatology · doi:10.1111/1346-8138.13284 · Cited by 68 · see citing works
Fatty Acid Oxidation in Peroxisomes: Enzymology, Metabolic Crosstalk with Other Organelles and Peroxisomal Disorders
Wanders, R. J. A., Vaz, F. M., Waterham, H. R., & Ferdinandusse, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-60204-8_5 · Cited by 67 · see citing works
Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene
Sevin, C., Ferdinandusse, S., Waterham, H. R., Wanders, R. J., & Aubourg, P. (2011) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-6-8 · Cited by 66 · see citing works
Dietary fat’gene interactions in cancer
Chen, Y. Q., Edwards, I. J., Kridel, S. J., Thornburg, T., & Berquin, I. M. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9075-x · Cited by 65 · see citing works
RNA-Seq based genetic variant discovery provides new insights into controlling fat deposition in the tail of sheep
Bakhtiarizadeh, M. R., & Alamouti, A. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-70527-8 · Cited by 64 · see citing works
An overview of inborn errors of complex lipid biosynthesis and remodelling
Lamari, F., Mochel, F., & Saudubray, J. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9764-x · Cited by 63 · see citing works
Review article: the function and regulation of proteins involved in bile salt biosynthesis and transport
Pellicoro, A., & Faber, K. N. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03522.x · Cited by 63 · see citing works
Gene expression in the LNCaP human prostate cancer progression model: Progression associated expression in vitro corresponds to expression changes associated with prostate cancer progression in vivo
Chen, Q., Watson, J. T., Marengo, S. R., Decker, K., Coleman, I. M., Nelson, P. S., & Sikes, R. A. (2006) · Cancer Letters · doi:10.1016/j.canlet.2005.12.027 · Cited by 61 · see citing works
Design, Synthesis, and In Vitro Testing of α-Methylacyl-CoA Racemase Inhibitors
Carnell, A. J., Hale, I., Denis, S. W., Wanders, R. J. A., Isaacs, W. B., Wilson, B. A. P., & Ferdinandusse, S. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0702377 · Cited by 58 · see citing works
Utilization of Sterol Carrier Protein-2 by Phytanoyl-CoA 2-Hydroxylase in the Peroxisomal α Oxidation of Phytanic Acid
Mukherji, M., Kershaw, N. J., Schofield, C. J., Wierzbicki, A. S., & Lloyd, M. D. (2002) · Chemistry & Biology · doi:10.1016/s1074-5521(02)00139-4 · Cited by 58 · see citing works
Sequence variants of alpha-methylacyl-CoA racemase are associated with prostate cancer risk.
Zheng, S. L., Chang, B., Faith, D., Johnson, J. R., Isaacs, S. D., Hawkins, G. A., Turner, A. R., Wiley, K. E., Bleecker, E. R., Walsh, P. C., et al. (2002) · PubMed · Cited by 58 · see citing works
In brain mitochondria the branched-chain fatty acid phytanic acid impairs energy transduction and sensitizes for permeability transition
Schönfeld, P., Kahlert, S., & Reiser, G. (2004) · Biochemical Journal · doi:10.1042/bj20040583 · Cited by 55 · see citing works
Tremor and deep white matter changes in α-methylacyl-CoA racemase deficiency
Clarke, C. E., Alger, S., Preece, M. A., Burdon, M., Chavda, S. V., Denis, S. W., Ferdinandusse, S., & Wanders, R. J. A. (2004) · Neurology · doi:10.1212/01.wnl.0000132841.81250.b7 · Cited by 54 · see citing works
Therapy Insight: inborn errors of metabolism in adult neurology—a clinical approach focused on treatable diseases
Sedel, F., Lyon‐Caen, O., & Saudubray, J. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0494 · Cited by 53 · see citing works
Hereditary spastic paraparesis in adults associated with inborn errors of metabolism: A diagnostic approach
Sedel, F., Fontaine, B., Saudubray, J., & Lyon‐Caen, O. (2007) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-007-0745-1 · Cited by 51 · see citing works
Fibroblast studies documenting a case of peroxisomal 2‐methylacyl‐CoA racemase deficiency: possible link between racemase deficiency and malabsorption and vitamin K deficiency
Veldhoven, P. P. V., Meyhi, E., Squires, R. H., Fransen, M., Fournier, B., Brys, V., Bennett, M. J., & Mannaerts, G. P. (2001) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2001.00877.x · Cited by 51 · see citing works
The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview
García‐Cazorla, À., Mochel, F., Lamari, F., & Saudubray, J. (2014) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-014-9776-6 · Cited by 50 · see citing works
High-Throughput Screen Identifies Novel Inhibitors of Cancer Biomarker α-Methylacyl Coenzyme A Racemase (AMACR/P504S)
Wilson, B. A. P., Wang, H., Nacev, B. A., Mease, R. C., Liu, J. O., Pomper, M. G., & Isaacs, W. B. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0902 · Cited by 50 · see citing works
Stereochemistry of the peroxisomal branched-chain fatty acid α- and β-oxidation systems in patients suffering from different peroxisomal disorders
Ferdinandusse, S., Rusch, H., van Lint, A. E. M., Dacremont, G., Wanders, R. J. A., & Vreken, P. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30150-4 · Cited by 49 · see citing works
Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal α-methylacyl-CoA racemase deficiency
Ferdinandusse, S., Overmars, H., Denis, S. W., Waterham, H. R., Wanders, R. J. A., & Vreken, P. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32345-2 · Cited by 48 · see citing works
A novel Refsum-like disorder that maps to chromosome 20
Fiskerstrand, T., Knappskog, P. M., Majewski, J., Wanders, R. J. A., Boman, H., & Bindoff, L. A. (2008) · Neurology · doi:10.1212/01.wnl.0000333664.90605.23 · Cited by 48 · see citing works
α-Methylacyl-CoA Racemase from Mycobacterium tuberculosis
Savolainen, K., Bhaumik, P., Schmitz, W., Kotti, T. J., Conzelmann, E., Wierenga, R. K., & Hiltunen, J. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m409704200 · Cited by 48 · see citing works
Reinvestigation of Peroxisomal 3-Ketoacyl-CoA Thiolase Deficiency: Identification of the True Defect at the Level of d-Bifunctional Protein
Ferdinandusse, S., van Grunsven, E. G., Oostheim, W., Denis, S. W., Hogenhout, E. M., IJlst, L., van Roermund, C. W. T., Waterham, H. R., Goldfischer, S. L., & Wanders, R. J. A. (2002) · The American Journal of Human Genetics · doi:10.1086/340970 · Cited by 48 · see citing works
Role of peroxisomes in human lipid metabolism and its importance for neurological development
Wanders, R. J. A., & Poll-The, B. T. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2015.06.018 · Cited by 46 · see citing works
Peripheral neuropathy and inborn errors of metabolism in adults
Sedel, F., Barnérias, C., Dubourg, O., Desguerres, I., Lyon‐Caen, O., & Saudubray, J. (2007) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-007-0684-x · Cited by 45 · see citing works
Peroxisomal Multifunctional Protein-2 Deficiency Causes Motor Deficits and Glial Lesions in the Adult Central Nervous System
Huyghe, S., Schmalbruch, H., Hulshagen, L., Veldhoven, P. P. V., Baes, M. I., & Hartmann, D. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.041220 · Cited by 45 · see citing works
An adult onset case of alpha‐methyl‐acyl‐CoA racemase deficiency
Smith, E. H., Gavrilov, D. K., Oglesbee, D., Freeman, W. D., Vavra, M. W., Matern, D., & Tortorelli, S. (2010) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-010-9183-6 · Cited by 44 · see citing works
Alpha‐oxidation of 3‐methyl‐substituted fatty acids and its thiamine dependence
Casteels, M., Foulon, V., Mannaerts, G. P., & Veldhoven, P. P. V. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03534.x · Cited by 44 · see citing works
The Catalysis of the 1,1-Proton Transfer by α-Methyl-acyl-CoA Racemase Is Coupled to a Movement of the Fatty Acyl Moiety Over a Hydrophobic, Methionine-rich Surface
Bhaumik, P., Schmitz, W., Hassinen, A., Hiltunen, J. K., Conzelmann, E., & Wierenga, R. K. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.01.062 · Cited by 41 · see citing works
AMACR mutations cause late-onset autosomal recessive cerebellar ataxia
Dick, D. J., Horváth, R., & Chinnery, P. F. (2011) · Neurology · doi:10.1212/wnl.0b013e31821a4484 · Cited by 40 · see citing works
Peroxisomal disorders
Baumgartner, M. R., & Saudubray, J. M. (2002) · Seminars in Neonatology · doi:10.1053/siny.2001.0089 · Cited by 40 · see citing works
Smell testing: an additional tool for identification of adult Refsum's disease
Gibberd, F. B. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.026690 · Cited by 40 · see citing works
Syndromic retinitis pigmentosa.
Karuntu, J. S., Almushattat, H., Nguyen, X.-T.-A., Plomp, A. S., Wanders, R. J. A., Hoyng, C. B., van Schooneveld, M. J., Schalij-Delfos, N. E., Brands, M. M., Leroy, B. P., et al. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2024.101324 · Cited by 39 · see citing works
The role of α-methylacyl-CoA racemase in bile acid synthesis
Cuebas, D. A., PHILLIPS, C., Schmitz, W., Conzelmann, E., & Новиков, Д. К. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630801 · Cited by 39 · see citing works
Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: involvement of increased AR expression and decreased IGF1 expression.
Takahara, K., Azuma, H., Sakamoto, T., Kiyama, S., Inamoto, T., Ibuki, N., Nishida, T., Nomi, H., Ubai, T., Segawa, N., et al. (2009) · PubMed · Cited by 38 · see citing works
Molecular Genetic Studies of Human Chromosome 7 in Russell–Silver Syndrome
Nakabayashi, K., Fernandez, B. A., Teshima, I. E., Shuman, C. T., Proud, V. K., Curry, C. J., Chitayat, D. A., Grebe, T. A., Ming, J. E., Oshimura, M., et al. (2002) · Genomics · doi:10.1006/geno.2002.6695 · Cited by 38 · see citing works
Tysnd1 Deficiency in Mice Interferes with the Peroxisomal Localization of PTS2 Enzymes, Causing Lipid Metabolic Abnormalities and Male Infertility
Mizuno, Y., Ninomiya, Y., Nakachi, Y., Iseki, M., Iwasa, H., Akita, M., Tsukui, T., Shimozawa, N., Ito, C., Toshimori, K., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003286 · Cited by 37 · see citing works
Diagnosis of inherited disorders of liver metabolism
Clayton, P. T. (2003) · Journal of Inherited Metabolic Disease · doi:10.1023/a:1024429032116 · Cited by 37 · see citing works
Synthesis and use of isotope-labelled substrates for a mechanistic study on human α-methylacyl-CoA racemase 1A (AMACR; P504S)
Darley, D. J., Butler, D. S., Prideaux, S. J., Thornton, T. W., Wilson, A. D., Woodman, T. J., Threadgill, M. D., & Lloyd, M. D. (2008) · Organic & Biomolecular Chemistry · doi:10.1039/b815396e · Cited by 35 · see citing works
Straight‐chain acyl‐CoA oxidase deficiency presenting with dysmorphia, neurodevelopmental autistic‐type regression and a selective pattern of leukodystrophy
Kurian, M. A., Ryan, S. P., BESLEY, G. T. N., Wanders, R. J. A., & King, M. D. (2004) · Journal of Inherited Metabolic Disease · doi:10.1023/b:boli.0000016687.88818.6d · Cited by 34 · see citing works
Lysosomal and Peroxisomal Disorders
Thomas, P. K., & Goebel, H. H. (2005) · Elsevier eBooks · doi:10.1016/b978-0-7216-9491-7.50082-x · Cited by 34 · see citing works
Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
Biase, I. D., Tortorelli, S., Kratz, L. E., Steinberg, S. J., Cusmano‐Ozog, K. P., & Braverman, N. (2019) · Genetics in Medicine · doi:10.1038/s41436-019-0713-9 · Cited by 33 · see citing works
A new defect of peroxisomal function involving pristanic acid: a case report
McLean, B. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.72.3.396 · Cited by 33 · see citing works
The cholic acid extension study in Zellweger spectrum disorders: Results and implications for therapy
Klouwer, F. C. C., Koot, B. G. P., Berendse, K., Kemper, E. M., Ferdinandusse, S., Koelfat, K. V. K., Leníček, M., Vaz, F. M., Engelen, M., Jansen, P. L. M., et al. (2018) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12042 · Cited by 32 · see citing works
Current Knowledge on the Function of α-Methyl Acyl-CoA Racemase in Human Diseases
Kong, G., Lee, H., Tran, Q., Kim, C., Park, J., Kwon, S. H., Kim, S., & Park, J. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00153 · Cited by 31 · see citing works
Expression profiling identifies a novel alpha-methylacyl-CoA racemase exon with fumarate hydratase homology.
Shen-Ong, G. L. C., Feng, Y., & Troyer, D. A. (2003) · PubMed · Cited by 30 · see citing works
Plasma lipidomics as a diagnostic tool for peroxisomal disorders
Herzog, K., Pras‐Raves, M. L., Ferdinandusse, S., Vervaart, M. A. T., Luyf, A. C. M., van Kampen, A. H. C., Wanders, R. J. A., Waterham, H. R., & Vaz, F. M. (2017) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-017-0114-7 · Cited by 29 · see citing works

An adult onset case of alpha‐methyl‐acyl‐CoA racemase deficiency
Smith, E. H., Gavrilov, D. K., Oglesbee, D., Freeman, W. D., Vavra, M. W., Matern, D., & Tortorelli, S. (2010) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-010-9183-6 · Cited by 44 · see citing works
Neuropathy
(2008) · Springer eBooks · doi:10.1007/978-1-4020-6754-9_11338
α‐Methylacyl‐ CoA Racemase Deficiency in a Patient with Ataxia, Spasticity, and Segmental Dystonia
Rashedi, R., Gelderblom, M., Prilop, L., Bester, M., Haack, T. B., & Zittel, S. (2024) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.14176 · Cited by 1 · see citing works
Redefining the phenotype of alpha-methylacyl-CoA racemase (AMACR) deficiency
Klouwer, F. C. C., Roosendaal, S. D., Hollak, C. E. M., Langeveld, M., Poll‐The, B. T., van Sorge, A. J., Wolf, N. I., van der Knaap, M. S., & Engelen, M. (2024) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-024-03358-9 · Cited by 7 · see citing works
Relapsing encephalopathy in a patient with -methylacyl-CoA racemase deficiency
Thompson, S. A., Calvin, J., Hogg, S. L., Ferdinandusse, S., Wanders, R. J. A., & Barker, R. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2007.129478 · Cited by 48 · see citing works

Authors: Ferdinandusse, S., Denis, S., Clayton, P. T., Graham, A., Rees, J. E., Allen, J. T., McLean, B. N., Brown, A. Y., Vreken, P., Waterham, H. R., & Wanders, R. J. A.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Princess Royal Hospital (GB)
Southmead Hospital (GB)
Royal Cornwall Hospital (GB)
Corresponding author: Wanders, Ronald J.A.
ORCID: Ferdinandusse, Sacha
Clayton, Peter T.
McLean, Brendan N.
Waterham, Hans R.
Wanders, Ronald J.A.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2000-02
Volume: 24
Issue: 2
Pages: 188-191
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/72861
OpenAlex: W1971365801
Cited by: 262
References: 23
Citations by year: 2026: 5 · 2025: 8 · 2024: 13 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 14 · 2013: 13 · 2012: 9
FWCI: 4.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords: AMACR, Refsum disease, adrenomyeloneuropathy, pristanic acid, branched-chain fatty acids, peroxisomal beta-oxidation, pigmentary retinopathy, Charcot-Marie-Tooth disease, upper motor neuron signs, peroxisomal disorders
MeSH terms: Adult, Amino Acid Sequence, Animals, Cloning, Molecular, Escherichia coli, Female, Humans, Infant, Male, Middle Aged, Molecular Sequence Data, Recombinant Proteins, Hereditary Sensory and Motor Neuropathy, Sequence Alignment, Point Mutation, Sequence Homology, Amino Acid, Age of Onset, Amino Acid Substitution, Racemases and Epimerases, Peroxisomes, Mice, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Mutations in the gene encoding peroxisomal α-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks