MCID: PRX028
MIFTS: 52

Peroxisomal Acyl-Coa Oxidase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Endocrine diseases

Aliases & Classifications for Peroxisomal Acyl-Coa Oxidase Deficiency

MalaCards integrated aliases for Peroxisomal Acyl-Coa Oxidase Deficiency:

Name: Peroxisomal Acyl-Coa Oxidase Deficiency 54 12 50 24 25 56 71 13 42 14 69
Pseudoneonatal Adrenoleukodystrophy 50 24 25 29
Pseudoadrenoleukodystrophy 50 25 56
Pseudo-Nald 25 56 71
Straight-Chain Acyl-Coa Oxidase Deficiency 50 25
Pseudo-Neonatal Adrenoleukodystrophy 50 56
Adrenoleukodystrophy, Pseudoneonatal 71
Peroxisomal Acyl-Coenzyme a Oxidase 12
Acyl-Coa Oxidase Deficiency 69

Characteristics:

Orphanet epidemiological data:

56
peroxisomal acyl-coa oxidase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: adolescent,late childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
neurologic deterioration is severe after age 2 to 2.5 years


HPO:

32
peroxisomal acyl-coa oxidase deficiency:
Onset and clinical course infantile onset
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Peroxisomal Acyl-Coa Oxidase Deficiency

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 2971disease definitionperoxisomal acyl-coa oxidase deficiency is a rare neurodegenerative disorder that belongs to the group of inherited peroxisomal disorders and is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.epidemiologyacyl-coa oxidase deficiency is a rare disease with only 30-40 patients identified world-wide so far.clinical descriptionthe disease manifests in the neonatal period with hypotonia (92%) and seizures (91%) as dominant features. facial dysmorphism (50%) with hypertelorism, epicanthus, low nasal bridge, and low-set ears may be present. some children have polydactyly and hepatomegaly. psychomotor development is delayed, but children are usually able to walk and say a few words. however, neurological regression occurs usually at the age of 1-3 years (mean age: 28 months). hypotonia is replaced by hypertonia with hyperreflexia. epilepsy may become more severe and sensorineural hearing loss may appear. strabismus, nystagmus, and optic atrophy can also occur.etiologyperoxisomal acyl-coa oxidase deficiency is caused by mutations in the acox1 gene (17q25.1) encoding peroxisomal straight-chain acyl-coa oxidase.diagnostic methodsdiagnosis is based on laboratory studies revealing increased serum very-long chain fatty acids (vlcfa) and markedly reduced acyl-coa oxidase activity in fibroblasts. mri examination of the brain shows abnormal white matter signals. diagnosis can be confirmed by the presence of mutations in the acox1 gene.differential diagnosisdifferential diagnoses include usher syndrome (see this term) and all causes of neonatal hypotonia. the other peroxisomal disorders should also be discarded, especially neonatal adrenoleukodystrophy (see this term), which presents similar clinical manifestations.antenatal diagnosisantenatal diagnosis is possible through biochemical and/or molecular analysis of amniocytes or chorionic villus cells.genetic counselingtransmission is autosomal recessive. genetic counseling should be offered to the families of patients.management and treatmentno specific treatment is available. multidisciplinary supportive care should be offered.prognosisprognosis is unfavorable; death usually occurs at around 5 years from respiratory issues.visit the orphanet disease page for more resources. last updated: 2/4/2010

MalaCards based summary : Peroxisomal Acyl-Coa Oxidase Deficiency, also known as pseudoneonatal adrenoleukodystrophy, is related to d-bifunctional protein deficiency and adrenoleukodystrophy, and has symptoms including failure to thrive, optic atrophy and nystagmus. An important gene associated with Peroxisomal Acyl-Coa Oxidase Deficiency is ACOX1 (Acyl-CoA Oxidase 1), and among its related pathways/superpathways are Metabolism and fatty acid beta-oxidation (peroxisome). The drugs Acetylcysteine and alemtuzumab have been mentioned in the context of this disorder. Affiliated tissues include liver, brain and eye, and related phenotypes are homeostasis/metabolism and liver/biliary system

UniProtKB/Swiss-Prot : 71 Adrenoleukodystrophy, pseudoneonatal: A peroxisomal single-enzyme disorder of fatty acid beta-oxidation, resulting in clinical manifestations that remind neonatal adrenoleukodystrophy. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo- NALD is characterized by increased plasma levels of very-long chain fatty acids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.

Genetics Home Reference : 25 Peroxisomal acyl-CoA oxidase deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with peroxisomal acyl-CoA oxidase deficiency have weak muscle tone (hypotonia) and seizures. They may have unusual facial features, including widely spaced eyes (hypertelorism), a low nasal bridge, and low-set ears. Extra fingers or toes (polydactyly) or an enlarged liver (hepatomegaly) also occur in some affected individuals.

OMIM : 54
Peroxisomal acyl-CoA oxidase deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also D-bifunctional protein deficiency (261515), caused by mutation in the HSD17B4 gene (601860) on chromosome 5q2. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (see 601539) (Watkins et al., 1995). (264470)

Disease Ontology : 12 A peroxisomal disease that is characterized by hypotonia and seizures in the neonatal period and neurological regression in early infancy.

Related Diseases for Peroxisomal Acyl-Coa Oxidase Deficiency

Graphical network of the top 20 diseases related to Peroxisomal Acyl-Coa Oxidase Deficiency:



Diseases related to Peroxisomal Acyl-Coa Oxidase Deficiency

Symptoms & Phenotypes for Peroxisomal Acyl-Coa Oxidase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
delayed psychomotor development
dystonia
extensor plantar responses
seizures
mental retardation, severe
more
Abdomen- Gastroin testinal:
dysphagia

Neurologic- Behavioral Psychiatric Manifestations:
irritability
no social interaction
stereotypical movements

Head And Neck- Face:
frontal bossing

Abdomen- Liver:
abnormal liver function tests
hepatomegaly, mild
hepatic steatosis, diffuse
liver biopsy shows normal numbers of enlarged peroxisomes

Chest- Breasts:
inverted nipples (uncommon)

Head And Neck- Eyes:
optic atrophy
nystagmus
strabismus
tapetoretinal degeneration
pigmentary retinopathy
more
Head And Neck- Ears:
low-set ears
hearing loss, sensorineural, bilateral

Head And Neck- Nose:
depressed nasal bridge
broad nasal bridge

Head And Neck- Head:
brachycephaly

Laboratory- Abnormalities:
normal serum plasmalogen
increased plasma levels of very-long chain fatty acids (vlcfa)
decreased or absent peroxisome acyl-coa oxidase activity and protein


Clinical features from OMIM:

264470

Human phenotypes related to Peroxisomal Acyl-Coa Oxidase Deficiency:

56 32 (show all 49)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 56 32 frequent (33%) Frequent (79-30%) HP:0001508
2 optic atrophy 56 32 frequent (33%) Frequent (79-30%) HP:0000648
3 nystagmus 56 32 frequent (33%) Frequent (79-30%) HP:0000639
4 strabismus 56 32 frequent (33%) Frequent (79-30%) HP:0000486
5 myopia 56 32 frequent (33%) Frequent (79-30%) HP:0000545
6 intellectual disability, severe 56 32 hallmark (90%) Very frequent (99-80%) HP:0010864
7 hyperreflexia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001347
8 hepatomegaly 56 32 frequent (33%) Frequent (79-30%) HP:0002240
9 seizures 56 32 hallmark (90%) Very frequent (99-80%) HP:0001250
10 hypertonia 56 32 occasional (7.5%) Occasional (29-5%) HP:0001276
11 low-set ears 56 32 frequent (33%) Frequent (79-30%) HP:0000369
12 depressed nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0005280
13 hypertelorism 56 32 frequent (33%) Frequent (79-30%) HP:0000316
14 global developmental delay 56 32 hallmark (90%) Very frequent (99-80%) HP:0001263
15 hypodontia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000668
16 respiratory insufficiency 56 32 frequent (33%) Frequent (79-30%) HP:0002093
17 epicanthus 56 32 frequent (33%) Frequent (79-30%) HP:0000286
18 muscular hypotonia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001252
19 developmental regression 56 32 hallmark (90%) Very frequent (99-80%) HP:0002376
20 sensorineural hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000407
21 gait disturbance 56 32 hallmark (90%) Very frequent (99-80%) HP:0001288
22 abnormal electroretinogram 56 32 hallmark (90%) Very frequent (99-80%) HP:0000512
23 neurological speech impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0002167
24 eeg abnormality 56 32 hallmark (90%) Very frequent (99-80%) HP:0002353
25 abnormality of visual evoked potentials 56 32 hallmark (90%) Very frequent (99-80%) HP:0000649
26 abnormality of metabolism/homeostasis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001939
27 abnormality of nervous system morphology 56 32 hallmark (90%) Very frequent (99-80%) HP:0012639
28 hand polydactyly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001161
29 dysphagia 32 HP:0002015
30 dystonia 32 HP:0001332
31 tapetoretinal degeneration 32 HP:0000547
32 pigmentary retinopathy 32 HP:0000580
33 irritability 32 HP:0000737
34 frontal bossing 32 HP:0002007
35 neonatal hypotonia 32 HP:0001319
36 wide nasal bridge 32 HP:0000431
37 brachycephaly 32 HP:0000248
38 leukodystrophy 32 HP:0002415
39 death in infancy 56 Frequent (79-30%)
40 inverted nipples 32 HP:0003186
41 babinski sign 32 HP:0003487
42 elevated hepatic transaminases 32 HP:0002910
43 no social interaction 32 HP:0008763
44 severe global developmental delay 32 HP:0011344
45 intellectual disability, progressive 32 HP:0006887
46 bilateral sensorineural hearing impairment 32 HP:0008619
47 cns demyelination 32 HP:0007305
48 decreased light- and dark-adapted electroretinogram amplitude 32 HP:0000654
49 diffuse hepatic steatosis 32 HP:0006555

UMLS symptoms related to Peroxisomal Acyl-Coa Oxidase Deficiency:


seizures, abnormal pyramidal signs

MGI Mouse Phenotypes related to Peroxisomal Acyl-Coa Oxidase Deficiency:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.5 ACOX1 AGXT CAT HSD17B4 PEX5 PPARA
2 liver/biliary system MP:0005370 9.02 HSD17B4 PEX5 PPARA SCP2 ACOX1

Drugs & Therapeutics for Peroxisomal Acyl-Coa Oxidase Deficiency

Drugs for Peroxisomal Acyl-Coa Oxidase Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
id 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 Phase 2 52-24-4 5453
8 Tocopherol Approved, 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:


id 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 Peroxisomal Acyl-Coa Oxidase Deficiency

Cochrane evidence based reviews: peroxisomal acyl-coa oxidase deficiency

Genetic Tests for Peroxisomal Acyl-Coa Oxidase Deficiency

Genetic tests related to Peroxisomal Acyl-Coa Oxidase Deficiency:

id Genetic test Affiliating Genes
1 Pseudoneonatal Adrenoleukodystrophy 29 24 ACOX1

Anatomical Context for Peroxisomal Acyl-Coa Oxidase Deficiency

MalaCards organs/tissues related to Peroxisomal Acyl-Coa Oxidase Deficiency:

39
Liver, Brain, Eye, Testes

Publications for Peroxisomal Acyl-Coa Oxidase Deficiency

Articles related to Peroxisomal Acyl-Coa Oxidase Deficiency:

id Title Authors Year
1
Peroxisomal acyl-CoA-oxidase deficiency: two new cases. ( 18536048 )
2008
2
Peroxisomal acyl-CoA oxidase deficiency. ( 11815777 )
2002
3
Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. ( 8279468 )
1994
4
Pristanic acid does not accumulate in peroxisomal acyl-CoA oxidase deficiency: evidence for a distinct peroxisomal pristanyl-CoA oxidase. ( 1779614 )
1991

Variations for Peroxisomal Acyl-Coa Oxidase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Peroxisomal Acyl-Coa Oxidase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 ACOX1 p.Gly178Cys VAR_025789 rs118204091
2 ACOX1 p.Met278Val VAR_025790 rs118204090
3 ACOX1 p.Ser184Leu VAR_067041 rs780887410
4 ACOX1 p.Gly231Val VAR_067042
5 ACOX1 p.Gln309Arg VAR_067043 rs118204092
6 ACOX1 p.Ser310Pro VAR_067044 rs758962364

ClinVar genetic disease variations for Peroxisomal Acyl-Coa Oxidase Deficiency:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 ACOX1 nsv513791 deletion Pathogenic
2 ACOX1 NM_004035.6(ACOX1): c.832A> G (p.Met278Val) single nucleotide variant Pathogenic rs118204090 GRCh37 Chromosome 17, 73949644: 73949644
3 ACOX1 NM_004035.6(ACOX1): c.532G> T (p.Gly178Cys) single nucleotide variant Pathogenic rs118204091 GRCh37 Chromosome 17, 73953546: 73953546
4 ACOX1 NM_004035.6(ACOX1): c.926A> G (p.Gln309Arg) single nucleotide variant Pathogenic rs118204092 GRCh37 Chromosome 17, 73949550: 73949550
5 ACOX1 NM_004035.6(ACOX1): c.442C> T (p.Arg148Ter) single nucleotide variant Pathogenic rs118204093 GRCh37 Chromosome 17, 73953636: 73953636
6 ACOX1 NM_004035.6(ACOX1): c.372_389del18 (p.Phe124_Asn129del) deletion Pathogenic rs387906248 GRCh37 Chromosome 17, 73956337: 73956354
7 ACOX1 nsv513790 deletion Pathogenic
8 ACOX1 NM_004035.6(ACOX1): c.1851delT (p.Gly618Alafs) deletion Likely pathogenic rs797045080 GRCh38 Chromosome 17, 75948335: 75948335
9 ACOX1 NM_004035.6(ACOX1): c.176G> C (p.Arg59Pro) single nucleotide variant Likely pathogenic rs777937235 GRCh38 Chromosome 17, 75978627: 75978627

Expression for Peroxisomal Acyl-Coa Oxidase Deficiency

Search GEO for disease gene expression data for Peroxisomal Acyl-Coa Oxidase Deficiency.

Pathways for Peroxisomal Acyl-Coa Oxidase Deficiency

GO Terms for Peroxisomal Acyl-Coa Oxidase Deficiency

Cellular components related to Peroxisomal Acyl-Coa Oxidase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.73 ACOX1 AGXT CAT HSD17B4 PEX5 SCP2
2 intracellular membrane-bounded organelle GO:0043231 9.62 ACOX1 AGXT CAT SCP2
3 peroxisomal membrane GO:0005778 9.46 ACOX1 CAT HSD17B4 PEX5
4 peroxisomal matrix GO:0005782 9.35 ACOX1 AGXT CAT HSD17B4 SCP2
5 peroxisome GO:0005777 9.1 ACOX1 AGXT CAT HSD17B4 PEX5 SCP2

Biological processes related to Peroxisomal Acyl-Coa Oxidase Deficiency according to GeneCards Suite gene sharing:

(show all 12)
id Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.67 ACOX1 APOC3 HSD17B4 PPARA
2 regulation of lipid metabolic process GO:0019216 9.51 ACOX1 PPARA
3 fatty acid metabolic process GO:0006631 9.5 ACOX1 HSD17B4 PPARA
4 response to insulin GO:0032868 9.49 CAT PPARA
5 triglyceride metabolic process GO:0006641 9.48 APOC3 CAT
6 bile acid biosynthetic process GO:0006699 9.46 HSD17B4 SCP2
7 lipoprotein metabolic process GO:0042157 9.43 APOC3 PPARA
8 peroxisome organization GO:0007031 9.4 PEX5 SCP2
9 fatty acid beta-oxidation GO:0006635 9.33 ACOX1 HSD17B4 PEX5
10 very long-chain fatty acid metabolic process GO:0000038 9.26 ACOX1 HSD17B4
11 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.13 ACOX1 HSD17B4 SCP2
12 alpha-linolenic acid metabolic process GO:0036109 8.8 ACOX1 HSD17B4 SCP2

Molecular functions related to Peroxisomal Acyl-Coa Oxidase Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 9.33 APOC3 PPARA SCP2
2 receptor binding GO:0005102 9.02 ACOX1 AGXT CAT HSD17B4 SCP2
3 cholesterol binding GO:0015485 8.96 APOC3 SCP2

Sources for Peroxisomal Acyl-Coa Oxidase Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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