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

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

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.·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?

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
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
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 196
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
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
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
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
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
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
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 92

Flagged first, then by citations

Show all 23 references

Research works printed but not linked: 1

Steinberg, D. Refsum disease. in The Metabolic and Molecular Bases of Inherited Disease (eds Scriver, C.R., Beaudet, A.L., Sly, W.S. & Valle, D.) 2351–2369 (McGraw-Hill, New York, 1995).

Sorted by citations

Items 201–263 of 263

Variable clinical phenotypes of alpha‐methylacyl‐ CoA racemase deficiency: Report of four cases and review of the literature
Selamioğlu, A., Balcı, M. C., Karaca, M., Khalil, Y., Hirachan, R., Durmuş, H., Parman, Y., Gedikbaşı, A., Demirkol, M., Clayton, P. T., et al. (2024) · JIMD Reports · doi:10.1002/jmd2.12437 · Cited by 2
Utility of PIN4 cocktail antibody in the atypical foci of the Prostate
Chougani, S., Sunandalakshmi, G. V., Durga, K., Ravisankar, V., & Santhi, V. (2020) · International Journal of Clinical and Diagnostic Pathology · doi:10.33545/pathol.2020.v3.i1f.204 · Cited by 2
Association between a new 3q;5q chromosomal translocation and dystrophy of human retinal pigment epithelium.
Pereira, S. R. F., Silva, A. S., Bormann, E. P., & Kuppinger, O. (2007) · PubMed · Cited by 2
Tissue Distribution and Versatile Functions of PPARs
Youssef, J., & Badr, M. Z. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-420-3_5 · Cited by 2
Disorders of Bile Acid Synthesis and Biliary Transport
Lemonde, H. A., Gissen, P., & Clayton, P. T. (2014) · Springer eBooks · doi:10.1007/978-3-642-40337-8_34 · Cited by 2
Peroxisomal Disorders
Poll‐The, B. T., & Wanders, R. J. A. (2014) · Springer eBooks · doi:10.1007/978-3-642-40337-8_24 · Cited by 2
Peroxisomal Disorders
Wanders, R. J. A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00110-5 · Cited by 2
Peroxisomal Disorders
Shimozawa, N. (2019) · Springer eBooks · doi:10.1007/978-981-15-1169-1_5 · Cited by 2
Genetic control of age-related gene expression and complex traits in the human brainPreprint
Martin, T., & Fraser, H. B. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/125195 · Cited by 2
Bile Acids
Ferdinandusse, S., & Vaz, F. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-58819-8_14 · Cited by 1
Primary bile acid synthesis disorders
Васильевна, В. Г., Хавкин, А. И., Потапов, А. С., Андреевна, С. Т., Nikitin, A. V., & Gevorkyan, A. K. (2025) · Russian Journal of Evidence-Based Gastroenterology · doi:10.17116/dokgastro20251401171 · Cited by 1
Two cases of Zellweger spectrum disorder with PEX26 mutations in twins
Васильевна, В. Г., Андреевна, С. Т., & Nikitin, A. V. (2025) · Russian Journal of Evidence-Based Gastroenterology · doi:10.17116/dokgastro202514011118 · Cited by 1
Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease
Rayana, N. P., Gogna, N., Krebs, M. P., Collin, G. B., Naggert, J. Κ., & Nishina, P. M. (2026) · Mammalian Genome · doi:10.1007/s00335-026-10239-y · Cited by 1
AMACR Detection in Urine Samples. Lack of Clinical Application in Routine Practice~!2010-02-11~!2010-06-23~!2010-08-26~!
Małusecka, E., Gogler, A., Gawkowska‐Suwińska, M., Behrendt, K., Nowicka, E., Smolska-Ciszewska, B., & Zajusz, A. (2010) · The Open Prostate Cancer Journal · doi:10.2174/1876822901003010074 · Cited by 1
Bile Acids and Bile Flow
Setchell, K. D. R., & Kohli, R. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-37591-7.00002-1 · Cited by 1
Adult Refsum Disease (ARD)
Leroy, B. P. (2014) · Springer eBooks · doi:10.1007/978-3-540-69466-3_24 · Cited by 1
Peroxisomal Disorders
Raymond, G. V., Baranano, K. W., & Fatemi, A. S. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-0435-8.00038-x · Cited by 1
Autoantibody Positivity in Two Bahraini Siblings With a Novel Alpha-Methylacyl-CoA Racemase Mutation
Isa, H. M. A., Khudair, A. D., Marshall, R. A., Khudair, A. D., Rawahia, T. A., & Busehail, M. Y. (2023) · Cureus · doi:10.7759/cureus.41720 · Cited by 1
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
Genetic testing for Refsum disease
Abeshi, A., Zulian, A., Beccari, T., Dündar, M., D’Esposito, F., & Bertelli, M. (2017) · The EuroBiotech Journal · doi:10.24190/issn2564-615x/2017/s1.28 · Cited by 1
Neurometabolische Krankheiten mit neuropathologischen Befunden
Goebel, H. H. (2011) · Springer eBooks · doi:10.1007/978-3-642-02324-8_6 · Cited by 1
Mechanisms of Toxicity in Fatty Acid Oxidation Disorders
Sharer, J. D. (2009) · Wiley eBooks · doi:10.1002/9783527628100.ch13 · Cited by 1
Does α-methylacyl-CoA-racemase play an important role in perineural tumor invasion?
Gupta, R. S. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.05.003 · Cited by 1
Rare Cholesterol Related Disorders – A Sterolomic Library for Diagnosis and Monitoring of DiseasesPreprint
Asgari, M. A., Yutuc, E., Abdel‐Khalik, J., Crick, P. J., Morris, A. A. M., Jones, S. A., Ghosh, A., Curnock, R., Hart, C., Schöls, L. J., et al. (2025) · medRxiv · doi:10.1101/2025.06.23.25328695 · Cited by 1
Prenatal Diagnosis of the Peroxisomal and Mitochondrial Fatty Acid Oxidation Deficiencies
Wanders, R. J. A. (2009) · Wiley eBooks · doi:10.1002/9781444314342.ch13
History of PPAR Discovery
Youssef, J., & Badr, M. Z. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-420-3_2
The Liver in the Neonate, in Infancy, and Childhood
Siew, S., & Kelly, D. A. (2018) · doi:10.1002/9781119237662.ch31
UNIVERSIDADE FEDERAL DO RIO GRANDE DO SUL INSTITUTO DE CIÊNCIAS BÁSICAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS BIOLÓGICAS
Alegre, P. (2006)
α-Methylacyl-CoA racemase : an enzyme at crossroads in lipid metabolism
Savolainen, K. (2004)
Lipides du nerf périphérique
Baumann, N., & Aubry, J. (2004) · Encyclopédie médico-chirurgicale. Neurologie · doi:10.1016/s0246-0378(03)00131-3
Fatty Acid Metabolism in Skeletal Muscle and Nerve, and in Neuromuscular Disorders
Yao, J., & Rebouche, C. J. (2007) · Food science and technology · doi:10.1201/9781420006902.ch48
Bile acid abnormalities in peroxisomal disorders
Ferdinandusse, S., & Wanders, R. J. A. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9644-0_33
Enzyme Diagnostics in a Changing World of Exome Sequencing and Newborn Screening as Exemplified for Peroxisomal, Mitochondrial, and Lysosomal Disorders
Wanders, R. J. A., Poorthuis, B. J. H. M., & Rodenburg, R. J. (2016) · Springer eBooks · doi:10.1007/978-3-662-49410-3_38
Co nowego w cholestazie – część 3. Wrodzone zaburzenia syntezy kwasów żółciowych
Lipiński, P., Socha, P., & Jankowska, I. (2017) · Pediatria Polska · doi:10.1016/j.pepo.2017.03.013
Peroxisomal Disorders
Raymond, G. V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-410529-4.00064-4
Disorders of Bile Acid Synthesis and Metabolism in Children
Setchell, K. D. R., & Heubi, J. E. (2021) · Cambridge University Press eBooks · doi:10.1017/9781108918978.033
Prenatal Diagnosis of the Peroxisomal and Mitochondrial Fatty Acid Oxidation Deficiencies
Wanders, R. J. A., & Waterham, H. R. (2021) · doi:10.1002/9781119676980.ch24
Multifunctional roles of bile acid biosynthetic enzymes and the isolation of a new vitamin D 25-hydroxylase
Russell, D. W., & Cheng, J. B. (2007) · Springer eBooks · doi:10.1007/1-4020-2913-6_3
Lexikalischer Teil
Witköwski, R., Prokop, O., Ullrich, E., & Thiel, G. (2003) · Springer eBooks · doi:10.1007/978-3-642-55694-4_5
Peroxisomal disorders
Raymond, G. V. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813955-4.00068-4
Peroxisomale Krankheiten
Rosewich, H., & Gärtner, J. (2014) · Springer eBooks · doi:10.1007/978-3-642-45188-1_49
The Molecular Pathogenesis and Pathophysiology of Prostate Cancer
Nelson, W. G., & Marzo, A. M. D. (2006) · Translational medicine series · doi:10.3109/9781420019858.001
Genetic defects in sterol synthesis, absorption, and degradation into bile acids
Romeo, S. (2011) · doi:10.1093/med/9780199235292.003.1246
Peroxisomal Disorders
Poll‐The, B. T., Aubourg, P. R., & Wanders, R. J. A. (2006) · Springer eBooks · doi:10.1007/978-3-540-28785-8_40
Refsum Disease
(2005) · Springer eBooks · doi:10.1007/3-540-27660-2_22
Disorders of peroxisomal metabolism in adults
Wierzbicki, A. S. (2020) · doi:10.1093/med/9780198746690.003.0236
Thiamine Pyrophosphate
Casteels, M., Foulon, V., Mannaerts, G. P., & Veldhoven, P. V. (2003) · Oxidative stress and disease · doi:10.1201/9780203913420.ch29
Disorders of Bile Acid Synthesis
Clayton, P. T. (2006) · Springer eBooks · doi:10.1007/3-540-28962-3_34
Alpha-methyl acetyl-coA racemase deficiency. Magnetic resonance imaging findings of three patients with encephalopathy, epilepsy, and stroke-like episodes
Palacio-Montoya, M. I., Herrera, D. A., Vargas, S. A., & Castillo, M. (2023) · The Neuroradiology Journal · doi:10.1177/19714009231187342
ASYMPTOMATIC RETINAL DYSFUNCTION AND RETINAL ABNORMALITIES IN A PATIENT WITH ALPHA-METHYLACYL-COA RACEMASE DEFICIENCY
Kalogeropoulos, D., Lagha, L., & Lotery, A. J. (2024) · Retinal Cases & Brief Reports · doi:10.1097/icb.0000000000001549
Peroxisomal Biomarkers
Vaz, F. M., & Wanders, R. J. A. (2024) · Springer eBooks · doi:10.1007/978-3-031-58819-8_8
The key role of gas chromatography-mass spectrometry and molecular genetic analysis methods in the diagnosis of peroxisomal disorders in children
Mamedov, I. S., Perevesentsev, O. A., & Krapivkin, A. I. (2024) · Laboratory Service · doi:10.17116/labs20241303117
Bile Acid Physiology and Alterations in the Enterohepatic Circulation
Guthrie, G. J., & Harpavat, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-11760-2.00003-3
Emerging paradigms in diabetic neuropathy: Epigenetics, phytotherapy, machine-learning-based diagnostics and clinical trials of herbal interventions
Vashishta, P., Chauhan, M., & Asija, R. (2025) · Next research. · doi:10.1016/j.nexres.2025.101079
Alpha-methylacyl-CoA racemase (AMACR) deficiency: report on novel patient and literature review
Lipiński, P., Rusecka, J. M., Sobczyńska‐Tomaszewska, A., Vaz, F. M., Stradomska, T. J., & Tylki‐Szymańska, A. (2026) · Journal of Applied Genetics · doi:10.1007/s13353-026-01047-w
Altérations mitochondriales et processus inflammatoire dans la déficience en acyl- Coenzyme A oxydase 1 peroxysomale
Hajj, H. I. E. (2012) · theses.fr (ABES) · doi:10.70675/f64502b8zb0d3z4fe5zbc45z543a928be0cb
Mise en évidence de la diversité des populations de cactus (Opuntia spp.) au Maroc et de la modulation du métabolisme lipidique par des extraits naturels et de phytostérols issues de cactus ou d'huile d'Argan dans les cellules microgliales BV2
Kharrassi, Y. E. (2015) · theses.fr (ABES) · doi:10.70675/b4faa240z73eez450bz8332z946a77b3f157
Analyse de la régulation de l'homéostasie des acides biliaires au sein des testicules
Holota, H. (2024) · theses.fr (ABES) · doi:10.70675/87a97831z9d93z48dazb8b7z8e7a929fc132
Repurposing AMACR as a Precision Metabolic Target in Castration-Resistant Prostate Cancer
Singh, N. (2026) · Pharmaceutical science. · doi:10.5772/intechopen.1015493
Diagnosis and Metabolic Management of Adult Refsum Disease: Guidance From the Medical and Scientific Committee of Global DARE (Defeat Adult Refsum Everywhere)
Ramachandran, R., Buttigieg, R., Eichler, F., Leroy, B., Mahroo, O. A., Huckfeldt, R. M., Firman, S. J., Baldwin, E., DeMarco, K., Kuranoff, S., et al. (2026) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.70201
Human peroxisomal disorders—laboratory diagnosis
Dasouki, M. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-41379-7.00019-6
BindingDB Entry 2535: Design, synthesis, and in vitro testing of alpha-methylacyl-CoA racemase inhibitors.
BindingDB (2008) · UC San Diego · doi:10.7270/q2x065bt
Refsum Disease- a Disorder of Peroxisomal Alpha-oxidation
Wierzbicki, A. S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374105-9.00191-x

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

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks