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Alpha-methylacyl-CoA racemase deficiency(AMACRD)

MedGen UID:
482058
Concept ID:
C3280428
Disease or Syndrome
Synonyms: AMACR deficiency; AMACRD
SNOMED CT: Alpha-methylacyl-CoA racemase deficiency disorder (700463002); AMACR deficiency (700463002); Congenital bile acid synthesis defect type 4 (700463002)
 
Gene (location): AMACR (5p13.2)
 
Monarch Initiative: MONDO:0013681
OMIM®: 614307

Definition

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). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/alpha-methylacyl-coa-racemase-deficiency

Clinical features

From HPO
Abnormality of the liver
MedGen UID:
893061
Concept ID:
C4021780
Finding
An abnormality of the liver.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Migraine
MedGen UID:
57451
Concept ID:
C0149931
Disease or Syndrome
Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Intention tremor
MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Elevated circulating phytanic acid concentration
MedGen UID:
869360
Concept ID:
C4023786
Finding
An abnormal elevation of phytanic acid.
Increased circulating very long-chain fatty acid concentration
MedGen UID:
1788690
Concept ID:
C5539740
Finding
Increased concentration of very long-chain fatty acids in the blood circulation. Very long-chain fatty acids are fatty acids (FAs) with a chain-length of 22 or more carbons.
Increased phytanic acid:pristanic acid ratio
MedGen UID:
1841789
Concept ID:
C5826402
Finding
An elevation above the normal ratio of blood phytanic acid concentration to pristanic acid concentration.
Reduced alpha-methylacyl-CoA racemase activity in cultured fibroblasts
MedGen UID:
1054770
Concept ID:
CN376643
Finding
Activity of alpha-methylacyl-CoA racemase (AMACR; EC 5.1.99.4) below the lower limit of normal in cultured fibroblasts.
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Constriction of peripheral visual field
MedGen UID:
68613
Concept ID:
C0235095
Finding
An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
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  
  • CROGVAlpha-methylacyl-CoA racemase deficiency

Recent clinical studies

Etiology

Deka D, Chakravarty M
Mymensingh Med J 2024 Apr;33(2):636-642. PMID: 38557550
Alsalamah AK, Khan AO
Mol Vis 2021;27:396-402. Epub 2021 Jul 1 PMID: 34267495Free PMC Article
Ferdinandusse S, van Grunsven EG, Oostheim W, Denis S, Hogenhout EM, IJlst L, van Roermund CW, Waterham HR, Goldfischer S, Wanders RJ
Am J Hum Genet 2002 Jun;70(6):1589-93. Epub 2002 Apr 23 doi: 10.1086/340970. PMID: 11992265Free PMC Article
Ferdinandusse S, Overmars H, Denis S, Waterham HR, Wanders RJ, Vreken P
J Lipid Res 2001 Jan;42(1):137-41. PMID: 11160375
Ferdinandusse S, Denis S, IJlst L, Dacremont G, Waterham HR, Wanders RJ
J Lipid Res 2000 Nov;41(11):1890-6. PMID: 11060359

Diagnosis

Alsalamah AK, Khan AO
Mol Vis 2021;27:396-402. Epub 2021 Jul 1 PMID: 34267495Free PMC Article
Gündüz M, Ünal Ö, Küçükçongar-Yavaş A, Kasapkara Ç
Turk J Pediatr 2019;61(2):289-291. doi: 10.24953/turkjped.2019.02.023. PMID: 31951345
Haugarvoll K, Johansson S, Tzoulis C, Haukanes BI, Bredrup C, Neckelmann G, Boman H, Knappskog PM, Bindoff LA
Orphanet J Rare Dis 2013 Jan 3;8:1. doi: 10.1186/1750-1172-8-1. PMID: 23286897Free PMC Article
Sundaram SS, Bove KE, Lovell MA, Sokol RJ
Nat Clin Pract Gastroenterol Hepatol 2008 Aug;5(8):456-68. Epub 2008 Jun 24 doi: 10.1038/ncpgasthep1179. PMID: 18577977Free PMC Article
Ferdinandusse S, Overmars H, Denis S, Waterham HR, Wanders RJ, Vreken P
J Lipid Res 2001 Jan;42(1):137-41. PMID: 11160375

Therapy

Li Y, Liu ML, Liang WB, Zhuo Y, He XJ
Biosens Bioelectron 2023 Oct 15;238:115589. Epub 2023 Aug 11 doi: 10.1016/j.bios.2023.115589. PMID: 37591158
Clarke CE, Alger S, Preece MA, Burdon MA, Chavda S, Denis S, Ferdinandusse S, Wanders RJ
Neurology 2004 Jul 13;63(1):188-9. doi: 10.1212/01.wnl.0000132841.81250.b7. PMID: 15249642

Prognosis

Wang Y, Zhao P, Wang L, Wang J, Ji X, Li Y, Shi H, Li Y, Zhang W, Jiang Y
Pathol Res Pract 2022 Jul;235:153960. Epub 2022 May 27 doi: 10.1016/j.prp.2022.153960. PMID: 35653922

Clinical prediction guides

Wang Y, Zhao P, Wang L, Wang J, Ji X, Li Y, Shi H, Li Y, Zhang W, Jiang Y
Pathol Res Pract 2022 Jul;235:153960. Epub 2022 May 27 doi: 10.1016/j.prp.2022.153960. PMID: 35653922
Raspollini MR, Castiglione F, Cheng L, Montironi R, Lopez-Beltran A
J Clin Pathol 2016 Jun;69(6):547-50. Epub 2016 Mar 3 doi: 10.1136/jclinpath-2015-203565. PMID: 26941183

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