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Carnitine acylcarnitine translocase deficiency(CACTD)

MedGen UID:
91000
Concept ID:
C0342791
Disease or Syndrome
Synonym: CACTD
SNOMED CT: Carnitine acylcarnitine translocase deficiency (238003000)
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): SLC25A20 (3p21.31)
 
Monarch Initiative: MONDO:0008918
OMIM®: 212138
Orphanet: ORPHA159

Disease characteristics

Excerpted from the GeneReview: Carnitine-Acylcarnitine Translocase Deficiency
Carnitine-acylcarnitine translocase (CACT) is a critical component of the carnitine shuttle, which facilitates the transfer of long-chain fatty acylcarnitines across the inner mitochondrial membrane. CACT deficiency causes a defect in mitochondrial long-chain fatty acid β-oxidation, with variable clinical severity. Severe neonatal-onset disease is most common, with symptoms evident within two days after birth; attenuated cases may present in the first months of life. Hyperammonemia and cardiac arrhythmia are prominent in early-onset disease, with high rates of cardiac arrest. Other clinical features are typical for disorders of long-chain fatty acid oxidation: poor feeding, lethargy, hypoketotic hypoglycemia, hypotonia, transaminitis, liver dysfunction with hepatomegaly, and rhabdomyolysis. Univentricular or biventricular hypertrophic cardiomyopathy, ranging from mild to severe, may respond to appropriate dietary and medical therapies. Hyperammonemia is difficult to treat and is an important determinant of long-term neurocognitive outcome. Affected individuals with early-onset disease typically experience brain injury at presentation, and have recurrent hyperammonemia leading to developmental delay / intellectual disability. Affected individuals with later-onset disease have milder symptoms and are less likely to experience recurrent hyperammonemia, allowing a better developmental outcome. Prompt treatment of the presenting episode to prevent hypoglycemic, hypoxic, or hyperammonemic brain injury may allow normal growth and development. [from GeneReviews]
Authors:
J Andres Morales Corado  |  Chung U Lee  |  Gregory M Enns   view full author information

Additional descriptions

From OMIM
Carnitine-acylcarnitine translocase deficiency is a rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy and arrhythmias, skeletal muscle damage, and liver dysfunction. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. However, presentations at a later age with a milder phenotype have been reported (summary by Rubio-Gozalbo et al., 2004).  http://www.omim.org/entry/212138
From MedlinePlus Genetics
Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Signs and symptoms of this disorder usually begin soon after birth and may include breathing problems, seizures, and an irregular heartbeat (arrhythmia). Affected individuals typically have low blood glucose (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CACT deficiency also usually have excess ammonia in the blood (hyperammonemia), an enlarged liver (hepatomegaly), and a weakened heart muscle (cardiomyopathy).

Many infants with CACT deficiency do not survive the newborn period. Some affected individuals have a less severe form of the condition and do not develop signs and symptoms until early childhood. These individuals are at risk for liver failure, nervous system damage, coma, and sudden death.  https://medlineplus.gov/genetics/condition/carnitine-acylcarnitine-translocase-deficiency

Clinical features

From HPO
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Atrioventricular block
MedGen UID:
13956
Concept ID:
C0004245
Disease or Syndrome
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
Cardiac arrest
MedGen UID:
5456
Concept ID:
C0018790
Finding
An abrupt loss of heart function.
Hypotension
MedGen UID:
5715
Concept ID:
C0020649
Finding
Low Blood Pressure, vascular hypotension.
Ventricular tachycardia
MedGen UID:
12068
Concept ID:
C0042514
Finding
A tachycardia originating in the ventricles characterized by rapid heart rate (over 100 beats per minute) and broad QRS complexes (over 120 ms).
Premature ventricular contraction
MedGen UID:
56236
Concept ID:
C0151636
Disease or Syndrome
Premature ventricular contractions (PVC) or ventricular extrasystoles are premature contractions of the heart that arise in response to an impulse in the ventricles rather than the normal impulse from the sinoatrial (SA) node.
Ventricular hypertrophy
MedGen UID:
87400
Concept ID:
C0340279
Disease or Syndrome
Enlargement of the cardiac ventricular muscle tissue with increase in the width of the wall of the ventricle and loss of elasticity. Ventricular hypertrophy is clinically differentiated into left and right ventricular hypertrophy.
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
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.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
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.
Rhabdomyolysis
MedGen UID:
19775
Concept ID:
C0035410
Pathologic Function
Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream.
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).
Cardiorespiratory arrest
MedGen UID:
154664
Concept ID:
C0600228
Pathologic Function
Cessation of breathing and/or cardiac function.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
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.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.
Reduced tissue carnitine-acylcarnitine translocase activity
MedGen UID:
1052924
Concept ID:
CN377406
Finding
Activity of carnitine-acylcarnitine translocase (CACT) in tissues below the lower limit of normal. CACT activity can be measured in multiple tissues.
Reduced circulating 6-pyruvoyltetrahydropterin synthase activity
MedGen UID:
1054536
Concept ID:
CN377407
Finding
The activity of 6-pyruvoyltetrahydropterin synthase in the blood circulation is below the lower limit of normal.

Professional guidelines

PubMed

Ryder B, Inbar-Feigenberg M, Glamuzina E, Halligan R, Vara R, Elliot A, Coman D, Minto T, Lewis K, Schiff M, Vijay S, Akroyd R, Thompson S, MacDonald A, Woodward AJM, Gribben JEL, Grunewald S, Belaramani K, Hall M, van der Haak N, Devanapalli B, Tolun AA, Wilson C, Bhattacharya K
J Inherit Metab Dis 2021 Jul;44(4):903-915. Epub 2021 Mar 29 doi: 10.1002/jimd.12371. PMID: 33634872
Norris MK, Scott AI, Sullivan S, Chang IJ, Lam C, Sun A, Hahn S, Thies JM, Gunnarson M, McKean KN, Merritt JL 2nd
JPEN J Parenter Enteral Nutr 2021 Feb;45(2):230-238. Epub 2020 Nov 11 doi: 10.1002/jpen.2034. PMID: 33085788
David J, Chrastina P, Pešková K, Kožich V, Friedecký D, Adam T, Hlídková E, Vinohradská H, Novotná D, Hedelová M, Al Taji E, Holubová A, Skalická V, Macek M, Gaillyová R, Votava F
Cent Eur J Public Health 2019 Jun;27(2):153-159. doi: 10.21101/cejph.a5441. PMID: 31241292

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased C16 and/or C18:1 Acylcarnitine, Carnitine Palmitoyltransferase II (CPT II) Deficiency and Carnitine Acylcarnitine Translocase (CACT) Deficiency, 2022

American College of Medical Genetics and Genomics, Algorithm, C16 +/- C18:1 Elevated: CPT II or CACT, 2022

Recent clinical studies

Etiology

Tang C, Tan M, Xie T, Tang F, Liu S, Wei Q, Liu J, Huang Y
Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Aug 25;50(4):463-471. doi: 10.3724/zdxbyxb-2021-0260. PMID: 34704419Free PMC Article
Habib A, Azize NAA, Rahman SA, Yakob Y, Suberamaniam V, Nazri MIBA, Abdullah Sani H, Ch'ng GS, Yin LH, Olpin S, Lock-Hock N
Clin Biochem 2021 Dec;98:48-53. Epub 2021 Oct 7 doi: 10.1016/j.clinbiochem.2021.10.002. PMID: 34626609
Ryder B, Inbar-Feigenberg M, Glamuzina E, Halligan R, Vara R, Elliot A, Coman D, Minto T, Lewis K, Schiff M, Vijay S, Akroyd R, Thompson S, MacDonald A, Woodward AJM, Gribben JEL, Grunewald S, Belaramani K, Hall M, van der Haak N, Devanapalli B, Tolun AA, Wilson C, Bhattacharya K
J Inherit Metab Dis 2021 Jul;44(4):903-915. Epub 2021 Mar 29 doi: 10.1002/jimd.12371. PMID: 33634872
Hui J, Tang NL, Li CK, Law LK, To KF, Yau P, Fung SL, Chong JS, Tsung L, Chiang G, Fung E, Cheung KL, Yeung WL, Fok TF
Pathology 2014 Aug;46(5):375-82. doi: 10.1097/PAT.0000000000000140. PMID: 24992243
Costa C, Costa JM, Slama A, Boutron A, Vequaud C, Legrand A, Brivet M
Mol Genet Metab 2003 Jan;78(1):68-73. doi: 10.1016/s1096-7192(02)00205-6. PMID: 12559850

Diagnosis

Habib A, Azize NAA, Rahman SA, Yakob Y, Suberamaniam V, Nazri MIBA, Abdullah Sani H, Ch'ng GS, Yin LH, Olpin S, Lock-Hock N
Clin Biochem 2021 Dec;98:48-53. Epub 2021 Oct 7 doi: 10.1016/j.clinbiochem.2021.10.002. PMID: 34626609
Yan HM, Hu H, Ahmed A, Feng BB, Liu J, Jia ZJ, Wang H
Medicine (Baltimore) 2017 Nov;96(45):e8549. doi: 10.1097/MD.0000000000008549. PMID: 29137068Free PMC Article
Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ
Mol Aspects Med 2004 Oct-Dec;25(5-6):521-32. doi: 10.1016/j.mam.2004.06.007. PMID: 15363639
Lopriore E, Gemke RJ, Verhoeven NM, Jakobs C, Wanders RJ, Roeleveld-Versteeg AB, Poll-The BT
Eur J Pediatr 2001 Feb;160(2):101-4. doi: 10.1007/s004310000644. PMID: 11271379
Pande SV
Am J Med Sci 1999 Jul;318(1):22-7. doi: 10.1097/00000441-199907000-00004. PMID: 10408757

Therapy

Habib A, Azize NAA, Rahman SA, Yakob Y, Suberamaniam V, Nazri MIBA, Abdullah Sani H, Ch'ng GS, Yin LH, Olpin S, Lock-Hock N
Clin Biochem 2021 Dec;98:48-53. Epub 2021 Oct 7 doi: 10.1016/j.clinbiochem.2021.10.002. PMID: 34626609
Ryder B, Inbar-Feigenberg M, Glamuzina E, Halligan R, Vara R, Elliot A, Coman D, Minto T, Lewis K, Schiff M, Vijay S, Akroyd R, Thompson S, MacDonald A, Woodward AJM, Gribben JEL, Grunewald S, Belaramani K, Hall M, van der Haak N, Devanapalli B, Tolun AA, Wilson C, Bhattacharya K
J Inherit Metab Dis 2021 Jul;44(4):903-915. Epub 2021 Mar 29 doi: 10.1002/jimd.12371. PMID: 33634872
Buist NR
Ann Nutr Metab 2016;68 Suppl 3:1-4. Epub 2016 Dec 9 doi: 10.1159/000448320. PMID: 27931034
Vatanavicharn N, Yamada K, Aoyama Y, Fukao T, Densupsoontorn N, Jirapinyo P, Sathienkijkanchai A, Yamaguchi S, Wasant P
Brain Dev 2015 Aug;37(7):698-703. Epub 2014 Nov 1 doi: 10.1016/j.braindev.2014.10.005. PMID: 25459972
Pierre G, Macdonald A, Gray G, Hendriksz C, Preece MA, Chakrapani A
J Inherit Metab Dis 2007 Oct;30(5):815. Epub 2007 May 12 doi: 10.1007/s10545-007-0518-x. PMID: 17508264

Prognosis

Zhang L, Hu Y, Xie M, Zhang Y, Cen K, Chen L, Cui Y, Li H, Wang D
J Int Med Res 2023 Apr;51(4):3000605231163811. doi: 10.1177/03000605231163811. PMID: 37115522Free PMC Article
Gürbüz BB, Yılmaz DY, Özgül RK, Koşukcu C, Dursun A, Sivri HS, Coşkun T, Tokatlı A
Turk J Pediatr 2021;63(4):691-696. doi: 10.24953/turkjped.2021.04.017. PMID: 34449152
Ryder B, Inbar-Feigenberg M, Glamuzina E, Halligan R, Vara R, Elliot A, Coman D, Minto T, Lewis K, Schiff M, Vijay S, Akroyd R, Thompson S, MacDonald A, Woodward AJM, Gribben JEL, Grunewald S, Belaramani K, Hall M, van der Haak N, Devanapalli B, Tolun AA, Wilson C, Bhattacharya K
J Inherit Metab Dis 2021 Jul;44(4):903-915. Epub 2021 Mar 29 doi: 10.1002/jimd.12371. PMID: 33634872
Yan HM, Hu H, Ahmed A, Feng BB, Liu J, Jia ZJ, Wang H
Medicine (Baltimore) 2017 Nov;96(45):e8549. doi: 10.1097/MD.0000000000008549. PMID: 29137068Free PMC Article
Lopriore E, Gemke RJ, Verhoeven NM, Jakobs C, Wanders RJ, Roeleveld-Versteeg AB, Poll-The BT
Eur J Pediatr 2001 Feb;160(2):101-4. doi: 10.1007/s004310000644. PMID: 11271379

Clinical prediction guides

Pasquadibisceglie A, Quadrotta V, Polticelli F
Int J Mol Sci 2023 Feb 15;24(4) doi: 10.3390/ijms24043946. PMID: 36835358Free PMC Article
Tang C, Tan M, Xie T, Tang F, Liu S, Wei Q, Liu J, Huang Y
Zhejiang Da Xue Xue Bao Yi Xue Ban 2021 Aug 25;50(4):463-471. doi: 10.3724/zdxbyxb-2021-0260. PMID: 34704419Free PMC Article
David J, Chrastina P, Pešková K, Kožich V, Friedecký D, Adam T, Hlídková E, Vinohradská H, Novotná D, Hedelová M, Al Taji E, Holubová A, Skalická V, Macek M, Gaillyová R, Votava F
Cent Eur J Public Health 2019 Jun;27(2):153-159. doi: 10.21101/cejph.a5441. PMID: 31241292
Tang C, Liu S, Wu M, Lin S, Lin Y, Su L, Zhang J, Feng Y, Huang Y
Clin Chim Acta 2019 Aug;495:476-480. Epub 2019 May 17 doi: 10.1016/j.cca.2019.05.018. PMID: 31108048
Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ
Mol Aspects Med 2004 Oct-Dec;25(5-6):521-32. doi: 10.1016/j.mam.2004.06.007. PMID: 15363639

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.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased C16 and/or C18:1 Acylcarnitine, Carnitine Palmitoyltransferase II (CPT II) Deficiency and Carnitine Acylcarnitine Translocase (CACT) Deficiency, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, C16 +/- C18:1 Elevated: CPT II or CACT, 2022

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