U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Acyl-CoA dehydrogenase 9 deficiency(MC1DN20)

MedGen UID:
1648400
Concept ID:
C4747517
Disease or Syndrome
Synonyms: Acyl-CoA dehydrogenase family, member 9, deficiency of; MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 20
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): ACAD9 (3q21.3)
 
Monarch Initiative: MONDO:0012624
OMIM®: 611126
Orphanet: ORPHA99901

Definition

MC1DN20 is an autosomal recessive multisystem disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack et al., 2010). For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. [from OMIM]

Additional description

From MedlinePlus Genetics
ACAD9 deficiency is a condition that varies in severity and can cause muscle weakness (myopathy), heart problems, and intellectual disability. Nearly all affected individuals have a buildup of a chemical called lactic acid in the body (lactic acidosis). Additional signs and symptoms that affect other body systems occur in rare cases.

Mildly affected individuals with ACAD9 deficiency usually experience nausea and extreme fatigue in response to physical activity (exercise intolerance). People with ACAD9 deficiency who are moderately affected have low muscle tone (hypotonia) and weakness in the muscles used for movement (skeletal muscles). Severely affected individuals have brain dysfunction combined with myopathy (encephalomyopathy); these individuals usually also have an enlarged and weakened heart muscle (hypertrophic cardiomyopathy), which is typically fatal in infancy or childhood.

Individuals with ACAD9 deficiency who survive past early childhood often have intellectual disability and may develop seizures. Rare signs and symptoms of ACAD9 deficiency include movement disorders and problems with liver and kidney function.

Some individuals with ACAD9 deficiency have had improvement in muscle strength and a reduction in lactic acid levels with treatment.  https://medlineplus.gov/genetics/condition/acad9-deficiency

Clinical features

From HPO
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Microvesicular hepatic steatosis
MedGen UID:
376784
Concept ID:
C1850415
Finding
A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes.
Cerebral edema
MedGen UID:
2337
Concept ID:
C0006114
Pathologic Function
Abnormal accumulation of fluid in the brain.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
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.
Decreased activity of mitochondrial complex I
MedGen UID:
393796
Concept ID:
C2677650
Finding
A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAcyl-CoA dehydrogenase 9 deficiency

Professional guidelines

PubMed

Lin Y, Zheng W, Chen Y, Huang C, Fu Q, Chen D, Peng W
Clin Chim Acta 2022 Dec 1;537:181-187. Epub 2022 Nov 5 doi: 10.1016/j.cca.2022.10.024. PMID: 36334790
Lüders A, Blankenstein O, Brockow I, Ensenauer R, Lindner M, Schulze A, Nennstiel U; the screening laboratories in Germany
Dtsch Arztebl Int 2021 Feb 19;118(7):101-108. doi: 10.3238/arztebl.m2021.0009. PMID: 33835005Free PMC Article
Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651

Recent clinical studies

Etiology

Lin Y, Zheng W, Chen Y, Huang C, Fu Q, Chen D, Peng W
Clin Chim Acta 2022 Dec 1;537:181-187. Epub 2022 Nov 5 doi: 10.1016/j.cca.2022.10.024. PMID: 36334790
Ambrose A, Sheehan M, Bahl S, Athey T, Ghai-Jain S, Chan A, Mercimek-Andrews S
Orphanet J Rare Dis 2022 Sep 15;17(1):360. doi: 10.1186/s13023-022-02512-5. PMID: 36109795Free PMC Article
Zheng W, Li X, Yang S, Luo C, Xiao F
Acta Neurol Belg 2022 Aug;122(4):969-977. Epub 2022 May 26 doi: 10.1007/s13760-022-01974-5. PMID: 35618995
Anderson DR, Viau K, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2020 Jan;129(1):13-19. Epub 2019 Nov 25 doi: 10.1016/j.ymgme.2019.11.006. PMID: 31836396
Béhin A, Acquaviva-Bourdain C, Souvannanorath S, Streichenberger N, Attarian S, Bassez G, Brivet M, Fouilhoux A, Labarre-Villa A, Laquerrière A, Pérard L, Kaminsky P, Pouget J, Rigal O, Vanhulle C, Eymard B, Vianey-Saban C, Laforêt P
Rev Neurol (Paris) 2016 Mar;172(3):231-41. Epub 2016 Mar 30 doi: 10.1016/j.neurol.2015.11.008. PMID: 27038534

Diagnosis

Lin Y, Zheng W, Chen Y, Huang C, Fu Q, Chen D, Peng W
Clin Chim Acta 2022 Dec 1;537:181-187. Epub 2022 Nov 5 doi: 10.1016/j.cca.2022.10.024. PMID: 36334790
Zheng W, Li X, Yang S, Luo C, Xiao F
Acta Neurol Belg 2022 Aug;122(4):969-977. Epub 2022 May 26 doi: 10.1007/s13760-022-01974-5. PMID: 35618995
Anderson DR, Viau K, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2020 Jan;129(1):13-19. Epub 2019 Nov 25 doi: 10.1016/j.ymgme.2019.11.006. PMID: 31836396
Muru K, Reinson K, Künnapas K, Lilleväli H, Nochi Z, Mosegaard S, Pajusalu S, Olsen RKJ, Õunap K
Mol Genet Genomic Med 2019 Sep;7(9):e915. Epub 2019 Aug 8 doi: 10.1002/mgg3.915. PMID: 31392824Free PMC Article
Andresen BS, Bross P, Jensen TG, Knudsen I, Winter V, Kølvraa S, Bolund L, Gregersen N
Scand J Clin Lab Invest Suppl 1995;220:9-25. PMID: 7652482

Therapy

Alhashem A, Mohamed S, Abdelraheem M, AlGufaydi B, Al-Aqeel A
Saudi Med J 2020 Jun;41(6):590-596. doi: 10.15537/smj.2020.6.25131. PMID: 32518924Free PMC Article
Muru K, Reinson K, Künnapas K, Lilleväli H, Nochi Z, Mosegaard S, Pajusalu S, Olsen RKJ, Õunap K
Mol Genet Genomic Med 2019 Sep;7(9):e915. Epub 2019 Aug 8 doi: 10.1002/mgg3.915. PMID: 31392824Free PMC Article
Ahrens-Nicklas RC, Pyle LC, Ficicioglu C
Genet Med 2016 Dec;18(12):1315-1319. Epub 2016 May 5 doi: 10.1038/gim.2016.49. PMID: 27148938Free PMC Article
Ferrari R, Merli E, Cicchitelli G, Mele D, Fucili A, Ceconi C
Ann N Y Acad Sci 2004 Nov;1033:79-91. doi: 10.1196/annals.1320.007. PMID: 15591005
Zhang J, Zhang W, Zou D, Chen G, Wan T, Zhang M, Cao X
Biochem Biophys Res Commun 2002 Oct 4;297(4):1033-42. doi: 10.1016/s0006-291x(02)02336-7. PMID: 12359260

Prognosis

Lin Y, Zheng W, Chen Y, Huang C, Fu Q, Chen D, Peng W
Clin Chim Acta 2022 Dec 1;537:181-187. Epub 2022 Nov 5 doi: 10.1016/j.cca.2022.10.024. PMID: 36334790
Rücklová K, Hrubá E, Pavlíková M, Hanák P, Farolfi M, Chrastina P, Vlášková H, Kousal B, Smolka V, Foltenová H, Adam T, Friedecký D, Ješina P, Zeman J, Kožich V, Honzík T
Nutrients 2021 Aug 24;13(9) doi: 10.3390/nu13092925. PMID: 34578803Free PMC Article
Eleftheriadou M, Medici-van den Herik E, Stuurman K, van Bever Y, Hellebrekers DMEI, van Slegtenhorst M, Ruijter G, Barakat TS
Mol Genet Genomic Med 2021 Feb;9(2):e1595. Epub 2021 Jan 11 doi: 10.1002/mgg3.1595. PMID: 33432785Free PMC Article
Lin Y, Peng W, Jiang M, Lin C, Lin W, Zheng Z, Li M, Fu Q
Clin Chim Acta 2018 Dec;487:133-138. Epub 2018 Sep 22 doi: 10.1016/j.cca.2018.09.033. PMID: 30253142
Van Hove JL, Zhang W, Kahler SG, Roe CR, Chen YT, Terada N, Chace DH, Iafolla AK, Ding JH, Millington DS
Am J Hum Genet 1993 May;52(5):958-66. PMID: 8488845Free PMC Article

Clinical prediction guides

Lin Y, Zheng W, Chen Y, Huang C, Fu Q, Chen D, Peng W
Clin Chim Acta 2022 Dec 1;537:181-187. Epub 2022 Nov 5 doi: 10.1016/j.cca.2022.10.024. PMID: 36334790
Alhashem A, Mohamed S, Abdelraheem M, AlGufaydi B, Al-Aqeel A
Saudi Med J 2020 Jun;41(6):590-596. doi: 10.15537/smj.2020.6.25131. PMID: 32518924Free PMC Article
Anderson DR, Viau K, Botto LD, Pasquali M, Longo N
Mol Genet Metab 2020 Jan;129(1):13-19. Epub 2019 Nov 25 doi: 10.1016/j.ymgme.2019.11.006. PMID: 31836396
Lin Y, Peng W, Jiang M, Lin C, Lin W, Zheng Z, Li M, Fu Q
Clin Chim Acta 2018 Dec;487:133-138. Epub 2018 Sep 22 doi: 10.1016/j.cca.2018.09.033. PMID: 30253142
Thorpe C, Kim JJ
FASEB J 1995 Jun;9(9):718-25. doi: 10.1096/fasebj.9.9.7601336. PMID: 7601336

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...