Deficiency of carnitine acetyltransferase

MedGen UID:: 257042
•Concept ID:: C1443228
•: Disease or Syndrome

Synonym:	CARNITINE ACETYLTRANSFERASE DEFICIENCY
SNOMED CT:	Deficiency of carnitine acetyltransferase (124257002)

Monarch Initiative:	MONDO:0011642
OMIM®:	606175

Definition

A disease arising from a defect of carnitine acetyltransferase causing disruption of whole-body glucose homeostasis and muscle-specific loss of function results in reduced metabolic control, which resembles the insulin resistant state. [from MONDO]

Recent clinical studies

Etiology

CRAT missense variants cause abnormal carnitine acetyltransferase function in an early-onset case of Leigh syndrome.

Laera L, Punzi G, Porcelli V, Gambacorta N, Trisolini L, Pierri CL, De Grassi A
Hum Mutat 2020 Jan;41(1):110-114. Epub 2019 Sep 23 doi: 10.1002/humu.23901. PMID: 31448845

Significance of l-carnitine for human health.

Adeva-Andany MM, Calvo-Castro I, Fernández-Fernández C, Donapetry-García C, Pedre-Piñeiro AM
IUBMB Life 2017 Aug;69(8):578-594. Epub 2017 Jun 26 doi: 10.1002/iub.1646. PMID: 28653367

The management of pregnancy and delivery in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

Pipitone A, Raval DB, Duis J, Vernon H, Martin R, Hamosh A, Valle D, Gunay-Aygun M
Am J Med Genet A 2016 Jun;170(6):1600-2. Epub 2016 Mar 21 doi: 10.1002/ajmg.a.37620. PMID: 26997609 Free PMC Article

The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins.

Davies MN, Kjalarsdottir L, Thompson JW, Dubois LG, Stevens RD, Ilkayeva OR, Brosnan MJ, Rolph TP, Grimsrud PA, Muoio DM
Cell Rep 2016 Jan 12;14(2):243-54. Epub 2015 Dec 31 doi: 10.1016/j.celrep.2015.12.030. PMID: 26748706 Free PMC Article

Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal.

Morillas M, López-Viñas E, Valencia A, Serra D, Gómez-Puertas P, Hegardt FG, Asins G
Biochem J 2004 May 1;379(Pt 3):777-84. doi: 10.1042/BJ20031373. PMID: 14711372 Free PMC Article

See all (12)

Diagnosis

CRAT missense variants cause abnormal carnitine acetyltransferase function in an early-onset case of Leigh syndrome.

Laera L, Punzi G, Porcelli V, Gambacorta N, Trisolini L, Pierri CL, De Grassi A
Hum Mutat 2020 Jan;41(1):110-114. Epub 2019 Sep 23 doi: 10.1002/humu.23901. PMID: 31448845

The management of pregnancy and delivery in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.

Pipitone A, Raval DB, Duis J, Vernon H, Martin R, Hamosh A, Valle D, Gunay-Aygun M
Am J Med Genet A 2016 Jun;170(6):1600-2. Epub 2016 Mar 21 doi: 10.1002/ajmg.a.37620. PMID: 26997609 Free PMC Article

Analytical approaches to determination of carnitine in biological materials, foods and dietary supplements.

Dąbrowska M, Starek M
Food Chem 2014 Jan 1;142:220-32. Epub 2013 Jul 18 doi: 10.1016/j.foodchem.2013.06.137. PMID: 24001835

Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency.

Hwu WL, Chien YH, Tang NL, Law LK, Lin CY, Lee NC
J Inherit Metab Dis 2007 Oct;30(5):816. Epub 2007 Aug 20 doi: 10.1007/s10545-007-0594-y. PMID: 17703373

Determination of free and total carnitine in plasma by an enzymatic reaction and spectrophotometric quantitation spectrophotometric determination of carnitine.

Prieto JA, Andrade F, Aldámiz-Echevarría L, Sanjurjo P
Clin Biochem 2006 Oct;39(10):1022-7. Epub 2006 Jul 13 doi: 10.1016/j.clinbiochem.2006.06.005. PMID: 16979615

See all (19)

Therapy

Prevention by L-carnitine of DNA damage induced by 3-hydroxy-3-methylglutaric and 3-methylglutaric acids and experimental evidence of lipid and DNA damage in patients with 3-hydroxy-3-methylglutaric aciduria.

Delgado CA, Balbueno Guerreiro GB, Diaz Jacques CE, de Moura Coelho D, Sitta A, Manfredini V, Wajner M, Vargas CR
Arch Biochem Biophys 2019 Jun 15;668:16-22. Epub 2019 Apr 30 doi: 10.1016/j.abb.2019.04.008. PMID: 31047871

Fatty Acid Oxidation and Its Relation with Insulin Resistance and Associated Disorders.

Lopaschuk GD
Ann Nutr Metab 2016;68 Suppl 3:15-20. Epub 2016 Dec 9 doi: 10.1159/000448357. PMID: 27931032

Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control.

Noland RC, Koves TR, Seiler SE, Lum H, Lust RM, Ilkayeva O, Stevens RD, Hegardt FG, Muoio DM
J Biol Chem 2009 Aug 21;284(34):22840-52. Epub 2009 Jun 24 doi: 10.1074/jbc.M109.032888. PMID: 19553674 Free PMC Article

Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency.

Hwu WL, Chien YH, Tang NL, Law LK, Lin CY, Lee NC
J Inherit Metab Dis 2007 Oct;30(5):816. Epub 2007 Aug 20 doi: 10.1007/s10545-007-0594-y. PMID: 17703373

A case of lipid storage myopathy with carnitine deficiency. Biochemical and electromyographic correlations.

Scarlato G, Albizzati MG, Bassi S, Cerri C, Frattola L
Eur Neurol 1977;16(1-6):222-9. doi: 10.1159/000114903. PMID: 615713

See all (7)

Prognosis

Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra.

Václavík J, Coene KLM, Vrobel I, Najdekr L, Friedecký D, Karlíková R, Mádrová L, Petsalo A, Engelke UFH, van Wegberg A, Kluijtmans LAJ, Adam T, Wevers RA
J Inherit Metab Dis 2018 May;41(3):407-414. Epub 2017 Nov 14 doi: 10.1007/s10545-017-0109-4. PMID: 29139026

Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control.

Deficiency of the carnitine transporter (OCTN2) with partial N-acetylglutamate synthase (NAGS) deficiency.

Hwu WL, Chien YH, Tang NL, Law LK, Lin CY, Lee NC
J Inherit Metab Dis 2007 Oct;30(5):816. Epub 2007 Aug 20 doi: 10.1007/s10545-007-0594-y. PMID: 17703373

Structural model of a malonyl-CoA-binding site of carnitine octanoyltransferase and carnitine palmitoyltransferase I: mutational analysis of a malonyl-CoA affinity domain.

Morillas M, Gómez-Puertas P, Rubí B, Clotet J, Ariño J, Valencia A, Hegardt FG, Serra D, Asins G
J Biol Chem 2002 Mar 29;277(13):11473-80. Epub 2002 Jan 14 doi: 10.1074/jbc.M111628200. PMID: 11790793

Muscle carnitine acetyltransferase and carnitine deficiency in a case of mitochondrial encephalomyopathy.

Melegh B, Seress L, Bedekovics T, Kispál G, Sümegi B, Trombitás K, Méhes K
J Inherit Metab Dis 1999 Oct;22(7):827-38. doi: 10.1023/a:1005562209034. PMID: 10518284

See all (7)