U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Acyl-CoA oxidase deficiency

MedGen UID:
376636
Concept ID:
C1849678
Disease or Syndrome
Synonyms: Peroxisomal acyl-CoA oxidase deficiency; Pseudoadrenoleukodystrophy; Pseudoneonatal adrenoleukodystrophy
SNOMED CT: Acyl-coenzyme A oxidase deficiency (238069004); Peroxisomal acyl-CoA oxidase deficiency (238069004); Straight-chain acyl-CoA oxidase deficiency (238069004); Pseudoadrenoleukodystrophy (238069004); Acyl-CoA oxidase deficiency (238069004); Pseudo-neonatal adrenoleucodystrophy (238069004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ACOX1 (17q25.1)
 
Monarch Initiative: MONDO:0009919
OMIM®: 264470
Orphanet: ORPHA2971

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
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.

Most babies with peroxisomal acyl-CoA oxidase deficiency learn to walk and begin speaking, but they experience a gradual loss of these skills (developmental regression), usually beginning between the ages of 1 and 3. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with peroxisomal acyl-CoA oxidase deficiency do not survive past early childhood.  https://medlineplus.gov/genetics/condition/peroxisomal-acyl-coa-oxidase-deficiency

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Diffuse hepatic steatosis
MedGen UID:
341511
Concept ID:
C1849686
Finding
A diffuse form of hepatic steatosis.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Bilateral sensorineural hearing impairment
MedGen UID:
96788
Concept ID:
C0452138
Disease or Syndrome
A bilateral form of sensorineural hearing impairment.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Intellectual disability, progressive
MedGen UID:
337397
Concept ID:
C1846149
Mental or Behavioral Dysfunction
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
No social interaction
MedGen UID:
376638
Concept ID:
C1849683
Finding
Lack of intentional participation in interactions with another person.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Very long chain fatty acid accumulation
MedGen UID:
481027
Concept ID:
C3279397
Finding
Reduced circulating acyl-CoA oxidase activity
MedGen UID:
1054168
Concept ID:
CN376730
Finding
The activity of acyl-CoA oxidase activity in the blood circulation is below the lower limit of normal.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Inversion of nipple
MedGen UID:
82844
Concept ID:
C0269269
Anatomical Abnormality
The presence of nipples that instead of pointing outward are retracted inwards.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Decreased light- and dark-adapted electroretinogram amplitude
MedGen UID:
326793
Concept ID:
C1839025
Finding
Descreased amplitude of eletrical response upon electroretinography.
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAcyl-CoA oxidase deficiency
Follow this link to review classifications for Acyl-CoA oxidase deficiency in Orphanet.

Professional guidelines

PubMed

Vogel BH, Bradley SE, Adams DJ, D'Aco K, Erbe RW, Fong C, Iglesias A, Kronn D, Levy P, Morrissey M, Orsini J, Parton P, Pellegrino J, Saavedra-Matiz CA, Shur N, Wasserstein M, Raymond GV, Caggana M
Mol Genet Metab 2015 Apr;114(4):599-603. Epub 2015 Feb 12 doi: 10.1016/j.ymgme.2015.02.002. PMID: 25724074
Schutgens RB, Schrakamp G, Wanders RJ, Heymans HS, Tager JM, van den Bosch H
J Inherit Metab Dis 1989;12 Suppl 1:118-34. doi: 10.1007/BF01799291. PMID: 2509803
Wanders RJ, van Wijland MJ, van Roermund CW, Schutgens RB, van den Bosch H, Tager JM, Nijenhuis A, Tromp A
Clin Chim Acta 1987 Jun 15;165(2-3):303-10. doi: 10.1016/0009-8981(87)90175-6. PMID: 3652452

Recent clinical studies

Etiology

Wanders RJ, Klouwer FC, Ferdinandusse S, Waterham HR, Poll-Thé BT
Methods Mol Biol 2017;1595:329-342. doi: 10.1007/978-1-4939-6937-1_30. PMID: 28409475
Ferdinandusse S, Denis S, Hogenhout EM, Koster J, van Roermund CW, IJlst L, Moser AB, Wanders RJ, Waterham HR
Hum Mutat 2007 Sep;28(9):904-12. doi: 10.1002/humu.20535. PMID: 17458872
Takahashi Y, Suzuki Y, Kumazaki K, Tanabe Y, Akaboshi S, Miura K, Shimozawa N, Kondo N, Nishiguchi T, Terada K, Orii T
Epilepsia 1997 Feb;38(2):182-8. doi: 10.1111/j.1528-1157.1997.tb01095.x. PMID: 9048670
Suzuki Y, Shimozawa N, Yajima S, Inoue K, Orii T, Kondo N
Jpn J Hum Genet 1996 Mar;41(1):167-75. doi: 10.1007/BF01892624. PMID: 8914632
Schutgens RB, Schrakamp G, Wanders RJ, Heymans HS, Tager JM, van den Bosch H
J Inherit Metab Dis 1989;12 Suppl 1:118-34. doi: 10.1007/BF01799291. PMID: 2509803

Diagnosis

Morita A, Enokizono T, Ohto T, Tanaka M, Watanabe S, Takada Y, Iwama K, Mizuguchi T, Matsumoto N, Morita M, Takashima S, Shimozawa N, Takada H
Brain Dev 2021 Mar;43(3):475-481. Epub 2020 Nov 21 doi: 10.1016/j.braindev.2020.10.011. PMID: 33234382
Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
Wanders RJ, Klouwer FC, Ferdinandusse S, Waterham HR, Poll-Thé BT
Methods Mol Biol 2017;1595:329-342. doi: 10.1007/978-1-4939-6937-1_30. PMID: 28409475
Takahashi Y, Suzuki Y, Kumazaki K, Tanabe Y, Akaboshi S, Miura K, Shimozawa N, Kondo N, Nishiguchi T, Terada K, Orii T
Epilepsia 1997 Feb;38(2):182-8. doi: 10.1111/j.1528-1157.1997.tb01095.x. PMID: 9048670
Schutgens RB, Schrakamp G, Wanders RJ, Heymans HS, Tager JM, van den Bosch H
J Inherit Metab Dis 1989;12 Suppl 1:118-34. doi: 10.1007/BF01799291. PMID: 2509803

Therapy

Heubi JE, Setchell KDR, Bove KE
Clin Liver Dis 2018 Nov;22(4):671-687. Epub 2018 Aug 22 doi: 10.1016/j.cld.2018.06.006. PMID: 30266156
Takahashi Y, Suzuki Y, Kumazaki K, Tanabe Y, Akaboshi S, Miura K, Shimozawa N, Kondo N, Nishiguchi T, Terada K, Orii T
Epilepsia 1997 Feb;38(2):182-8. doi: 10.1111/j.1528-1157.1997.tb01095.x. PMID: 9048670

Prognosis

Kawai H, Takashima S, Ohba A, Toyoshi K, Kubota K, Ohnishi H, Shimozawa N
Brain Dev 2023 Jan;45(1):58-69. Epub 2022 Oct 29 doi: 10.1016/j.braindev.2022.10.001. PMID: 36511274
Wang RY, Monuki ES, Powers J, Schwartz PH, Watkins PA, Shi Y, Moser A, Shrier DA, Waterham HR, Nugent DJ, Abdenur JE
J Inherit Metab Dis 2014 Sep;37(5):791-9. Epub 2014 Mar 12 doi: 10.1007/s10545-014-9698-3. PMID: 24619150Free PMC Article
Suzuki Y, Shimozawa N, Yajima S, Inoue K, Orii T, Kondo N
Jpn J Hum Genet 1996 Mar;41(1):167-75. doi: 10.1007/BF01892624. PMID: 8914632
Suzuki Y, Shimozawa N, Yajima S, Tomatsu S, Kondo N, Nakada Y, Akaboshi S, Lai M, Tanabe Y, Hashimoto T
Am J Hum Genet 1994 Jan;54(1):36-43. PMID: 8279468Free PMC Article

Clinical prediction guides

Kawai H, Takashima S, Ohba A, Toyoshi K, Kubota K, Ohnishi H, Shimozawa N
Brain Dev 2023 Jan;45(1):58-69. Epub 2022 Oct 29 doi: 10.1016/j.braindev.2022.10.001. PMID: 36511274
Carrozzo R, Bellini C, Lucioli S, Deodato F, Cassandrini D, Cassanello M, Caruso U, Rizzo C, Rizza T, Napolitano ML, Wanders RJ, Jakobs C, Bruno C, Santorelli FM, Dionisi-Vici C, Bonioli E
Am J Med Genet A 2008 Jul 1;146A(13):1676-81. doi: 10.1002/ajmg.a.32298. PMID: 18536048
Ferdinandusse S, Denis S, Hogenhout EM, Koster J, van Roermund CW, IJlst L, Moser AB, Wanders RJ, Waterham HR
Hum Mutat 2007 Sep;28(9):904-12. doi: 10.1002/humu.20535. PMID: 17458872
Espeel M, Depreter M, Nardacci R, D'Herde K, Kerckaert I, Stefanini S, Roels F
Microsc Res Tech 1997 Dec 1;39(5):453-66. doi: 10.1002/(SICI)1097-0029(19971201)39:5<453::AID-JEMT8>3.0.CO;2-H. PMID: 9408912
Fournier B, Saudubray JM, Benichou B, Lyonnet S, Munnich A, Clevers H, Poll-The BT
J Clin Invest 1994 Aug;94(2):526-31. doi: 10.1172/JCI117365. PMID: 8040306Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...