MCID: PRX028
MIFTS: 52

Peroxisomal Acyl-Coa Oxidase Deficiency

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

Aliases & Classifications for Peroxisomal Acyl-Coa Oxidase Deficiency

MalaCards integrated aliases for Peroxisomal Acyl-Coa Oxidase Deficiency:

Name: Peroxisomal Acyl-Coa Oxidase Deficiency 53 12 49 24 55 71 13 41 14 69
Pseudoneonatal Adrenoleukodystrophy 53 49 24 28
Straight-Chain Acyl-Coa Oxidase Deficiency 53 49 24
Pseudoadrenoleukodystrophy 49 24 55
Pseudo-Nald 24 55 71
Pseudo-Neonatal Adrenoleukodystrophy 49 55
Adrenoleukodystrophy, Pseudoneonatal 71
Peroxisomal Acyl-Coenzyme a Oxidase 12
Acyl-Coenzyme a Oxidase Deficiency 24
Acyl-Coa Oxidase Deficiency 69

Characteristics:

Orphanet epidemiological data:

55
peroxisomal acyl-coa oxidase deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: adolescent,late childhood;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
peroxisomal acyl-coa oxidase deficiency:
Mortality/Aging death in infancy
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Peroxisomal Acyl-Coa Oxidase Deficiency

NIH Rare Diseases : 49 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 seizures, hypertelorism and low-set ears. 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

OMIM : 53 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)

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 : 24 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.

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:

53
Neurologic Central Nervous System:
seizures
dystonia
leukodystrophy
extensor plantar responses
mental retardation, severe
more
Head And Neck Face:
frontal bossing

Abdomen Gastroin testinal:
dysphagia

Head And Neck Head:
brachycephaly

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 Ears:
low-set ears
hearing loss, sensorineural, bilateral

Head And Neck Eyes:
nystagmus
optic atrophy
strabismus
pigmentary retinopathy
tapetoretinal degeneration
more
Head And Neck Nose:
depressed nasal bridge
broad nasal bridge

Neurologic Behavioral Psychiatric Manifestations:
irritability
no social interaction
stereotypical movements

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:

55 31 (showing 49, show less)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
3 low-set ears 55 31 frequent (33%) Frequent (79-30%) HP:0000369
4 nystagmus 55 31 frequent (33%) Frequent (79-30%) HP:0000639
5 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
6 gait disturbance 55 31 hallmark (90%) Very frequent (99-80%) HP:0001288
7 hyperreflexia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001347
8 failure to thrive 55 31 frequent (33%) Frequent (79-30%) HP:0001508
9 respiratory insufficiency 55 31 frequent (33%) Frequent (79-30%) HP:0002093
10 neurological speech impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0002167
11 eeg abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0002353
12 developmental regression 55 31 hallmark (90%) Very frequent (99-80%) HP:0002376
13 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
14 hepatomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0002240
15 depressed nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0005280
16 sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000407
17 optic atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0000648
18 abnormality of visual evoked potentials 55 31 hallmark (90%) Very frequent (99-80%) HP:0000649
19 hypertonia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001276
20 intellectual disability, severe 55 31 hallmark (90%) Very frequent (99-80%) HP:0010864
21 abnormality of metabolism/homeostasis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001939
22 strabismus 55 31 frequent (33%) Frequent (79-30%) HP:0000486
23 epicanthus 55 31 frequent (33%) Frequent (79-30%) HP:0000286
24 abnormality of nervous system morphology 55 31 hallmark (90%) Very frequent (99-80%) HP:0012639
25 abnormal electroretinogram 55 31 hallmark (90%) Very frequent (99-80%) HP:0000512
26 myopia 55 31 frequent (33%) Frequent (79-30%) HP:0000545
27 hand polydactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001161
28 hypodontia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000668
29 dystonia 31 HP:0001332
30 frontal bossing 31 HP:0002007
31 dysphagia 31 HP:0002015
32 wide nasal bridge 31 HP:0000431
33 neonatal hypotonia 31 HP:0001319
34 brachycephaly 31 HP:0000248
35 irritability 31 HP:0000737
36 death in infancy 55 Frequent (79-30%)
37 severe global developmental delay 31 HP:0011344
38 elevated hepatic transaminases 31 HP:0002910
39 inverted nipples 31 HP:0003186
40 babinski sign 31 HP:0003487
41 intellectual disability, progressive 31 HP:0006887
42 leukodystrophy 31 HP:0002415
43 pigmentary retinopathy 31 HP:0000580
44 tapetoretinal degeneration 31 HP:0000547
45 bilateral sensorineural hearing impairment 31 HP:0008619
46 no social interaction 31 HP:0008763
47 diffuse hepatic steatosis 31 HP:0006555
48 cns demyelination 31 HP:0007305
49 decreased light- and dark-adapted electroretinogram amplitude 31 HP:0000654

UMLS symptoms related to Peroxisomal Acyl-Coa Oxidase Deficiency:


abnormal pyramidal signs, seizures

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

43 (showing 2, show less)
# 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 ACOX1 HSD17B4 PEX5 PPARA SCP2

Drugs & Therapeutics for Peroxisomal Acyl-Coa Oxidase Deficiency

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

(showing 21, show less)
# 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:

(showing 1, show less)

# 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:

# Genetic test Affiliating Genes
1 Pseudoneonatal Adrenoleukodystrophy 28 ACOX1

Anatomical Context for Peroxisomal Acyl-Coa Oxidase Deficiency

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

38
Liver, Brain, Eye, Testes

Publications for Peroxisomal Acyl-Coa Oxidase Deficiency

Articles related to Peroxisomal Acyl-Coa Oxidase Deficiency:

(showing 4, show less)
# 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 (showing 6, show less)
# 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 (showing 9, show less)
# 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 GRCh37 Chromosome 17, 73974708: 73974708

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:

(showing 5, show less)
# 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:

(showing 12, show less)
# 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:

(showing 3, show less)
# 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
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
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