PMID- 10655068
OWN - NLM
STAT- MEDLINE
DCOM- 20000228
LR  - 20091119
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 24
IP  - 2
DP  - 2000 Feb
TI  - Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause
      adult-onset sensory motor neuropathy.
PG  - 188-91
AB  - 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.
FAU - Ferdinandusse, S
AU  - Ferdinandusse S
AD  - Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical
      Center, University of Amsterdam, The Netherlands.
FAU - Denis, S
AU  - Denis S
FAU - Clayton, P T
AU  - Clayton PT
FAU - Graham, A
AU  - Graham A
FAU - Rees, J E
AU  - Rees JE
FAU - Allen, J T
AU  - Allen JT
FAU - McLean, B N
AU  - McLean BN
FAU - Brown, A Y
AU  - Brown AY
FAU - Vreken, P
AU  - Vreken P
FAU - Waterham, H R
AU  - Waterham HR
FAU - Wanders, R J
AU  - Wanders RJ
LA  - eng
SI  - GENBANK/AF158378
SI  - GENBANK/H19271
SI  - GENBANK/H19272
SI  - GENBANK/U89905
SI  - GENBANK/U89906
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Recombinant Proteins)
RN  - EC 5.1.- (Racemases and Epimerases)
RN  - EC 5.1.99.4 (alpha-methylacyl-CoA racemase)
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Cloning, Molecular
MH  - Escherichia coli
MH  - Female
MH  - Hereditary Sensory and Motor Neuropathy/*enzymology/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - Peroxisomes/*enzymology
MH  - *Point Mutation
MH  - Racemases and Epimerases/chemistry/*genetics/metabolism
MH  - Rats
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
EDAT- 2000/02/02 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/02 09:00
PHST- 2000/02/02 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/02 09:00 [entrez]
AID - 10.1038/72861 [doi]
PST - ppublish
SO  - Nat Genet. 2000 Feb;24(2):188-91. doi: 10.1038/72861.