Carnitine Palmitoyl Transferase, Type 1A (CPT1A)

The Arctic Variant

  • Amber Lee Madrid Patson Texas Christian University

Abstract

Carnitine Palmitoyl Transferase 1A (CPT1A) is a crucial enzyme needed for mitochondrial fatty acid oxidation and is fundamental for appropriate metabolic responses to prolonged fasting. Under normal conditions, the human body guarantees a constant energy supply, by metabolizing glucose in the short term and by oxidizing fatty acids into ketones during long term fasting or starvation. Fasting induces breakdown of the hepatic glycogen supply into glucose. Continued fasting eventually leads to glycogen depletion followed by a decrease in serum glucose and insulin levels, this decrease then activates hormone-sensitive lipases located in adipose tissues and causes the release of free fatty acids into the blood. Normally these free fatty acids would undergo beta-oxidation to produce energy, but CPT1A deficiency results in an 80% decrease in the activity of the CPT1A enzyme, leading to significant hepatic glycogen depletion and the inability to utilize ketones during periods of fasting. Preoperative fasting in these patients may result in vomiting, lethargy, hypoketotic hypoglycemia, seizures, liver failure, increased risk for infectious illnesses and higher rates of respiratory illnesses, placing this population at greater perioperative risk for anesthesia and surgery. Interventions include, but are not limited to, parent education and prevention techniques, recognition of symptoms, prompt treatment with glucose and even surgery cancellation. CPT1A deficiency is found in circum-arctic populations such as Alaskan Inupiat and Yupik, Canadian and Greenland Inuit, and Siberian Yupik and is thus known as the “Arctic Variant” of CPT1A. Once thought of as a rare disorder, the introduction of tandem mass spectrometry (MS/MS) to Alaska newborn screenings in 2003 revealed that the polymorphism c.1436C>T variant in the CPT1A gene has an incidence as high as 80% in specific regions of Alaska. As of 2011, an estimated 700 Alaska Native Infants born each year are homozygous for the c.1436C>T Arctic Variant. It is therefore important for anesthesia professionals in Alaska and other arctic regions to understand what CPT1A Arctic Variant is, and its implications for these patients in the perioperative period.

References

References
1) Hirschfeld, M. The arctic variant of CPT-1A. Yukon-Kuskokwim Health Corporation. Retrieved from: https://yk-health.org/images/3/36/Arctic-Variant-CPT-1.pdf Accessed February 1, 2019.
2) Koeller, D. Use of dried blood spots to study the arctic variant of CPT1A. Newborn Screening Translational Research Network. Retrieved from: https://nbstrn.org/sites/default/files/Koeller.pdf
Published April 25, 2013. Accessed January 27, 2019.
3) Gessner BD, Gillingham MB, Johnson MA, et al. Prevalence and distribution of the c.1436C-->T sequence variant of carnitine palmitoyltransferase 1A among Alaska Native infants. J Pediatr.
2011;158(1):124-129. doi:10.1016/j.jpeds.2010.07.031.
4) Gillingham MB, Hirschfeld M, Lowe S, et al. Impaired fasting tolerance among Alaska Native children with a common carnitine palmitoyltransferase 1A sequence variant. Mol Genet Metab.
2011;104(3):261-264. doi:10.1016/j.ymgme.2011.06.017.
5) Clemente FJ, Cardona A, Inchley CE, et al. A selective sweep on a deleterious mutation in CPT1A in Arctic populations. Am J Hum Genet. 2014;95(5):584-589. doi:10.1016/j.ajhg.2014.09.016.
6) Adeva-Andany MM, Calvo-Castro I, Fernandez-Fernandez C, Donapetry-Garcia C, Pedre-Pineiro AM. Significance of l-carnitine for human health. IUBMB Life. 2017;69(8):578-594.
doi:10.1002/iub.1646.PMID:28653367.
7) Rufer AC, Thoma R, Hennig M. Structural insight into function and regulation of carnitine palmitoyltransferase. Cell Mol Life Sci. 2009;66(15):2489-2501. doi:10.1007/s00018-009-0035-1.
8) Guyton, A. C, & Hall, J. E. (2016). Textbook of medical physiology-13th edition. Chapter 68 and 69. Philadelphia: Elsevier.
9) Gessner BD, Wood T, Johnson MA, Richards CS, Koeller DM. Evidence for an association between infant mortality and homozygosity for the arctic variant of carnitine palmitoyltransferase 1A.
Genet Med. 2016;18(9):933-939. doi:10.1038/gim.2015.197.
10) Koeller, D. Diet and the CPT1A arctic variant: impact on the health of Alaska Native children. Newborn Screening Translational Research Network. Retrieved from:
https://www.nbstrn.org/sites/default/files/nbstrn_6.1.17_koeller.pdf Published June 14, 2017. Accessed January 28, 2019.
11) Gessner BD, Gillingham MB, Wood T, Koeller DM. Association of a genetic variant of carnitine palmitoyltransferase 1A with infections in Alaska Native children. J Pediatr. 2013;163(6):1716-
1721. doi:10.1016/j.jpeds.2013.07.010.
12) Fatty Acid Oxidation Disorders: Carnitine palmitoyl transferase, type 1A arctic variant. Screening, Technology and Research in Genetics (STAR-G), Expanded Newborn Screening Using New
Technologies. Financial, Ethical, Legal and Social Issues (FELSI). Retrieved from: https://www.newbornscreening.info/Parents/fattyaciddisorders/CPT1AV.html#5 Updated December 18,
2014. Accessed March 2, 2019.
13) Jardine, B, Hirschfeld, M, Schumacher, A. Alaska Native Medical Center. Pocket guide to Alaska Native pediatric diagnoses: review of diagnoses rarely seen in other populations. Retrieved
from: http://anmc.org/files/Pocket-Guide-to-Alaska-Native-Pediatric-Diagnoses_web-1.pdf Published Spring 2016. Accessed February 26, 2019.
14) Syed, F, Turner, H, Alghamdi, F, Tumin, D, Tobias, J, Wani, T. Anesthetic management of a patient with carnitine-acylcarnitine translocase deficiency. N Am J
Med Case. doi:https://doi.org/10.14740/jmc3044w
15) Lemas DJ, Wiener HW, O'Brien DM, et al. Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup’ik
Eskimos. Journal of lipid research. 2012;53(1):175-184. doi:10.1194/jlr.P018952.PMID:22045927.
Published
2019-09-04
How to Cite
PATSON, Amber Lee Madrid. Carnitine Palmitoyl Transferase, Type 1A (CPT1A). Anesthesia eJournal, [S.l.], v. 7, p. 19-20, sep. 2019. ISSN 2333-2611. Available at: <https://anesthesiaejournal.com/index.php/aej/article/view/126>. Date accessed: 17 nov. 2019.
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