MCID: ALP012
MIFTS: 46

Alpha-Methylacyl-Coa Racemase Deficiency

Categories: Genetic diseases, Metabolic diseases

Aliases & Classifications for Alpha-Methylacyl-Coa Racemase Deficiency

MalaCards integrated aliases for Alpha-Methylacyl-Coa Racemase Deficiency:

Name: Alpha-Methylacyl-Coa Racemase Deficiency 53 12 24 71 28 13 14 69
Amacr Deficiency 53 12 24 71
Amacrd 53 71
Alpha-Methylacyl-Coa Racemase 13

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
onset usually in second decade
acute encephalopathic episodes may occur


HPO:

31
alpha-methylacyl-coa racemase deficiency:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Alpha-Methylacyl-Coa Racemase Deficiency

Genetics Home Reference : 24 Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder that causes a variety of neurological problems that begin in adulthood and slowly get worse. People with AMACR deficiency may have a gradual loss in intellectual functioning (cognitive decline), seizures, and migraines. They may also have acute episodes of brain dysfunction (encephalopathy) similar to stroke, involving altered consciousness and areas of damage (lesions) in the brain. Other features of AMACR deficiency may include weakness and loss of sensation in the limbs due to nerve damage (sensorimotor neuropathy), muscle stiffness (spasticity), and difficulty coordinating movements (ataxia). Vision problems caused by deterioration of the light-sensitive layer at the back of the eye (the retina) can also occur in this disorder.

MalaCards based summary : Alpha-Methylacyl-Coa Racemase Deficiency, also known as amacr deficiency, is related to bile acid synthesis defect, congenital, 4 and blood group--diego system, and has symptoms including ataxia, tremor and spasticity. An important gene associated with Alpha-Methylacyl-Coa Racemase Deficiency is AMACR (Alpha-Methylacyl-CoA Racemase), and among its related pathways/superpathways are Metabolism and Synthesis of bile acids and bile salts. The drugs Acetylcysteine and alemtuzumab have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and retina, and related phenotypes are homeostasis/metabolism and liver/biliary system

Disease Ontology : 12 A peroxisomal disease that has_material_basis in homozygous mutation in the AMACR gene on chromosome 5p13.2-q11.1. It is characterized by retinitis pigmentosa resulting in progressive visual failure, learning difficulties, a peripheral neuropathy, and hypogonadism.

OMIM : 53 AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging. Serum pristanic acid and C27 bile acid intermediates are increased (summary by Smith et al., 2010). (614307)

UniProtKB/Swiss-Prot : 71 Alpha-methylacyl-CoA racemase deficiency: A rare autosomal recessive peroxisomal disorder characterized by elevated plasma concentrations of pristanic acid C27-bile-acid intermediates, and adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging.

Related Diseases for Alpha-Methylacyl-Coa Racemase Deficiency

Graphical network of the top 20 diseases related to Alpha-Methylacyl-Coa Racemase Deficiency:



Diseases related to Alpha-Methylacyl-Coa Racemase Deficiency

Symptoms & Phenotypes for Alpha-Methylacyl-Coa Racemase Deficiency

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
spasticity
migraine
status epilepticus
cerebellar ataxia (1 patient)
more
Head And Neck Eyes:
visual impairment
pigmentary retinopathy (variable)

Abdomen Liver:
no liver disease

Laboratory Abnormalities:
increased serum pristanic acid
normal or increased serum phytanic acid
increased serum c26-bile-acid intermediates

Neurologic Behavioral Psychiatric Manifestations:
depression

Neurologic Peripheral Nervous System:
sensorimotor neuropathy

Endocrine Features:
primary hypogonadism (in 2 male patients)


Clinical features from OMIM:

614307

Human phenotypes related to Alpha-Methylacyl-Coa Racemase Deficiency:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 occasional (7.5%) HP:0001251
2 tremor 31 occasional (7.5%) HP:0001337
3 spasticity 31 HP:0001257
4 visual impairment 31 HP:0000505
5 migraine 31 HP:0002076
6 hypergonadotropic hypogonadism 31 HP:0000815
7 sensorimotor neuropathy 31 HP:0007141
8 status epilepticus 31 HP:0002133
9 pigmentary retinopathy 31 frequent (33%) HP:0000580
10 depressivity 31 HP:0000716

UMLS symptoms related to Alpha-Methylacyl-Coa Racemase Deficiency:


muscle spasticity, seizures

MGI Mouse Phenotypes related to Alpha-Methylacyl-Coa Racemase Deficiency:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.56 SCP2 SLC45A2 ACAA1 ACOX1 AMACR CYP46A1
2 liver/biliary system MP:0005370 9.02 ACOX1 AMACR HSD17B4 PHYH SCP2

Drugs & Therapeutics for Alpha-Methylacyl-Coa Racemase Deficiency

Drugs for Alpha-Methylacyl-Coa Racemase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcysteine Approved, Investigational Phase 2 616-91-1 12035
2
alemtuzumab Approved, Investigational Phase 2 216503-57-0
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
5
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
6
rituximab Approved Phase 2 174722-31-7 10201696
7 Thiotepa Approved, Investigational Phase 2 52-24-4 5453
8 Tocopherol Approved, Investigational, Nutraceutical Phase 2
9
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
10 Alkylating Agents Phase 2
11 Antilymphocyte Serum Phase 2
12 Antimetabolites Phase 2
13 Antimetabolites, Antineoplastic Phase 2
14 Immunosuppressive Agents Phase 2
15 N-monoacetylcystine Phase 2
16 Thioctic Acid Phase 2
17 Tocopherols Phase 2
18 Tocotrienols Phase 2
19 Vitamins Phase 2
20 Alpha-lipoic Acid Nutraceutical Phase 2
21 Tocotrienol Investigational, Nutraceutical Phase 2 6829-55-6

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)

Search NIH Clinical Center for Alpha-Methylacyl-Coa Racemase Deficiency

Genetic Tests for Alpha-Methylacyl-Coa Racemase Deficiency

Genetic tests related to Alpha-Methylacyl-Coa Racemase Deficiency:

# Genetic test Affiliating Genes
1 Alpha-Methylacyl-Coa Racemase Deficiency 28 AMACR

Anatomical Context for Alpha-Methylacyl-Coa Racemase Deficiency

MalaCards organs/tissues related to Alpha-Methylacyl-Coa Racemase Deficiency:

38
Brain, Eye, Retina, Liver

Publications for Alpha-Methylacyl-Coa Racemase Deficiency

Articles related to Alpha-Methylacyl-Coa Racemase Deficiency:

# Title Authors Year
1
MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing. ( 23286897 )
2013
2
Incidental finding of alpha-methylacyl-CoA racemase deficiency in a patient with oculocutaneous albinism type 4. ( 22987308 )
2012
3
Relapsing rhabdomyolysis due to peroxisomal alpha-methylacyl-coa racemase deficiency. ( 20921516 )
2010
4
Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency. ( 18032455 )
2008
5
Tremor and deep white matter changes in alpha-methylacyl-CoA racemase deficiency. ( 15249642 )
2004
6
A mouse model for alpha-methylacyl-CoA racemase deficiency: adjustment of bile acid synthesis and intolerance to dietary methyl-branched lipids. ( 15016763 )
2004
7
Plasma analysis of di- and trihydroxycholestanoic acid diastereoisomers in peroxisomal alpha-methylacyl-CoA racemase deficiency. ( 11160375 )
2001

Variations for Alpha-Methylacyl-Coa Racemase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Alpha-Methylacyl-Coa Racemase Deficiency:

71
# Symbol AA change Variation ID SNP ID
1 AMACR p.Ser52Pro VAR_010661 rs121917814

ClinVar genetic disease variations for Alpha-Methylacyl-Coa Racemase Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 AMACR NM_014324.5(AMACR): c.154T> C (p.Ser52Pro) single nucleotide variant Pathogenic rs121917814 GRCh37 Chromosome 5, 34007971: 34007971

Expression for Alpha-Methylacyl-Coa Racemase Deficiency

Search GEO for disease gene expression data for Alpha-Methylacyl-Coa Racemase Deficiency.

Pathways for Alpha-Methylacyl-Coa Racemase Deficiency

Pathways related to Alpha-Methylacyl-Coa Racemase Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.7 ACAA1 ACOX1 AKR1D1 AMACR CYP46A1 HACL1
2
Show member pathways
11.96 AKR1D1 AMACR CYP46A1 HSD17B4 SCP2
3 11.44 ACAA1 ACOX1 SCP2
4 11.42 ACAA1 ACOX1 AMACR HACL1 HSD17B4 PHYH
5
Show member pathways
11.28 ACAA1 ACOX1 HSD17B4 SCP2
6
Show member pathways
11.14 ACAA1 ACOX1
7
Show member pathways
11.1 ACAA1 ACOX1 HSD17B4 SCP2
8
Show member pathways
10.89 ACAA1 ACOX1 AMACR HACL1 HSD17B4 PHYH
9 10.85 ACAA1 SCP2

GO Terms for Alpha-Methylacyl-Coa Racemase Deficiency

Cellular components related to Alpha-Methylacyl-Coa Racemase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.72 ACOX1 AMACR HSD17B4 PHYH SCP2
2 intracellular membrane-bounded organelle GO:0043231 9.63 ACAA1 ACOX1 AMACR CYP46A1 HACL1 SCP2
3 peroxisome GO:0005777 9.5 ACAA1 ACOX1 AMACR HACL1 HSD17B4 PHYH
4 peroxisomal membrane GO:0005778 9.26 ACOX1 HSD17B4
5 peroxisomal matrix GO:0005782 9.17 ACAA1 ACOX1 AMACR HACL1 HSD17B4 PHYH

Biological processes related to Alpha-Methylacyl-Coa Racemase Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.85 ACOX1 AKR1D1 CYP46A1 HSD17B4 PHYH
2 lipid metabolic process GO:0006629 9.8 ACAA1 ACOX1 AKR1D1 CYP46A1 HSD17B4
3 fatty acid metabolic process GO:0006631 9.63 ACAA1 ACOX1 AMACR HACL1 HSD17B4 PHYH
4 alpha-linolenic acid metabolic process GO:0036109 9.56 ACAA1 ACOX1 HSD17B4 SCP2
5 fatty acid beta-oxidation GO:0006635 9.54 ACAA1 ACOX1 HSD17B4
6 androgen metabolic process GO:0008209 9.51 AKR1D1 HSD17B4
7 very long-chain fatty acid metabolic process GO:0000038 9.5 ACAA1 ACOX1 HSD17B4
8 bile acid metabolic process GO:0008206 9.49 ACAA1 AMACR
9 cholesterol catabolic process GO:0006707 9.48 AKR1D1 CYP46A1
10 fatty acid alpha-oxidation GO:0001561 9.43 HACL1 PHYH
11 bile acid biosynthetic process GO:0006699 9.35 AKR1D1 AMACR CYP46A1 HSD17B4 SCP2
12 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.02 ACAA1 ACOX1 AMACR HSD17B4 SCP2

Molecular functions related to Alpha-Methylacyl-Coa Racemase Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.46 ACAA1 HACL1 PHYH SCP2
2 oxidoreductase activity GO:0016491 9.35 ACOX1 AKR1D1 CYP46A1 HSD17B4 PHYH
3 cofactor binding GO:0048037 9.32 HACL1 PHYH
4 transferase activity, transferring acyl groups other than amino-acyl groups GO:0016747 9.26 ACAA1 SCP2
5 receptor binding GO:0005102 9.02 ACOX1 AMACR HACL1 HSD17B4 SCP2

Sources for Alpha-Methylacyl-Coa Racemase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....