Relapsing encephalopathy in a patient with  -methylacyl-CoA racemase deficiency

Thompson, Sian; Calvin, J.; Hogg, Sarah; Ferdinandusse, Sacha; Wanders, Ronald J. A.; Barker, Roger A.

doi:10.1136/jnnp.2007.129478

Cited by 41 publications

(20 citation statements)

References 9 publications

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“…The product of AMACR , alpha-methyl-CoA racemase, plays a pivotal role in lipid and bile acid metabolism. AMACR deficiency (MIM 604489) can lead to the toxic accumulation of metabolic intermediates in tissues and blood plasma, most notably pristanic acid via the α-oxidation pathway, characterized by adult onset of neurodegenerative symptoms, including sensory motor neuropathy, pigmentary retinopathy, seizures, and neurocognitive impairment [Thompson et al, 2007]. In one documented patient, AMACR deficiency was comorbid with schizophrenia, displaying elevated plasma pristanic acid levels and neurologic deficits resembling stroke-like episodes [Kapina et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

Kos

Carless

Peralta

et al. 2017

American J of Med Genetics Pt B

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Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR<0.1, association was detected for rs10941112 (P=2.1×10−5; q-value=0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (P=5.5×10−4), including brain tissue data from the Genotype-Tissue Expression project (minimum P=6.0×10−5). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (P=2.8×10−5; q-value=0.073). Protein-protein interactions among our top gene-based association results (P<0.05; n=359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (P=3.0×10−5), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance.

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Section: Discussionmentioning

confidence: 99%

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

Kos

Carless

Peralta

et al. 2017

American J of Med Genetics Pt B

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“…[2][3][4][5][6] Although each patient exhibited different clinical features, neurologic symptoms including seizures, peripheral neuropathy, altered mental status, and relapsing encephalitis were common among the adults. The reason for clinical relapses is unclear, although oxidative stresses, such as minor surgeries, may precipitate the release of pristanic acid from tissue stores.…”

Section: Case Reportmentioning

confidence: 98%

FUNDUS FINDINGS IN a PATIENT WITH Α-Methlyacyl-Coa RACEMASE DEFICIENCY

Stewart¹,

Vavra²,

Whaley³

2011

RETINAL Cases &Amp; Brief Reports

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“…AMACR deficiency has been described in several patients, mainly adults with a late-onset sensorimotor neuropathy, epilepsy, encephalopathy, pyramidal tract signs and migraine [4][5][6][7][8]. AMACR deficiency can also appear in the neonatal period with coagulopathy and mild cholestasis due to bile acid abnormalities [9].…”

Section: Introductionmentioning

confidence: 99%

Neurochemical Evidence that Pristanic Acid Impairs Energy Production and Inhibits Synaptic Na+, K+-ATPase Activity in Brain of Young Rats

et al. 2011

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Pristanic acid (Prist) accumulates in some peroxisomal disorders characterized by neurologic dysfunction and brain abnormalities. The present work investigated the in vitro effects of Prist on important parameters of energy metabolism in brain cortex of young rats. CO(2) production from labeled acetate and the activities of the respiratory chain complexes I-IV, creatine kinase and synaptic Na(+), K(+)-ATPase were measured. Prist decreased CO(2) production and the activities of complexes I, II and II-III. Prist also reduced Na(+), K(+)-ATPase activity, but did not affect the activity of creatine kinase. Considering the importance of the citric acid cycle and the electron flow through the respiratory chain for brain energy production and of Na(+), K(+)-ATPase for the maintenance of membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission. It is presumed that these pathomechanisms may be involved in the neurological damage found in patients affected by disorders in which Prist accumulates.

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Relapsing encephalopathy in a patient with -methylacyl-CoA racemase deficiency

Cited by 41 publications

References 9 publications

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

Exome sequences of multiplex, multigenerational families reveal schizophrenia risk loci with potential implications for neurocognitive performance

FUNDUS FINDINGS IN a PATIENT WITH Α-Methlyacyl-Coa RACEMASE DEFICIENCY

Neurochemical Evidence that Pristanic Acid Impairs Energy Production and Inhibits Synaptic Na+, K+-ATPase Activity in Brain of Young Rats

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