NORD gratefully acknowledges Susan Winter, MD, Medical Director of Medical Genetics/Metabolism, Valley Children's Hospital, Madera, California, for assistance in the preparation of this report.
Carnitine palmitoyltransferase 1A deficiency (CPT1A) is characterized by a sudden onset of liver failure and damage to the nervous system resulting from liver failure (hepatic encephalopathy), usually associated with fasting or illness. CPT1A deficiency is caused by an abnormality (mutation) in the CPT1A gene that results in the production of an abnormally functioning carnitine palmitoyltransferase 1 enzyme and decreased metabolism of long-chain fatty acids. CPT1A deficiency is inherited as an autosomal recessive genetic disorder.
Three types of CPT1A deficiency have been recognized: The hepatic encephalopathy type usually occurs in children and is associated with a low level of ketones in the blood, low blood sugar (hypoglycemia), enlarged liver, muscle weakness and elevated carnitine in the blood. The adult-onset myopathy type is characterized by a sudden onset of muscle cramping associated with exercise without low blood sugar or liver dysfunction. The third type is acute fatty liver of pregnancy that occurs when a pregnant woman with one abnormal CPT1A gene carries a fetus with two abnormal CPT1A genes and is associated with liver failure in the mother.
CPT1A deficiency is caused by a mistake in the code for the CPT1A gene (mutation) resulting in decreased carnitine palmitoyltransferase 1 enzyme activity preventing normal metabolism of long-chain fatty acids from food and stored fat and decreased energy production.
CPT1A deficiency is inherited as an autosomal recessive genetic disorder with a 25% recurrence risk for future children to be affected. Autosomal recessive genetic diseases occur when each parent carries a mutation on the same gene (carrier) and each parent passes the mutated gene on to the child, giving the child no normal gene to compensate for the mutations.
If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry nearly 30 gene mutations. Usually, the parents do not match on the genes mutated and the children cannot be affected. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to be carrying the same abnormal gene, increasing their risk to have children with a recessive genetic disorder.
CPT1A deficiency has been reported in approximately 30-40 individuals. The incidence of this condition may be higher in the Hutterite populations in the northern United States and Canada and the Inuit populations in northern Canada, Alaska and Greenland. This condition occurs with equal frequency in males and females.
CPT1A deficiency is diagnosed by a combination of physical symptoms and laboratory testing. The typical laboratory findings include low levels of ketones, elevated liver transaminases, elevated ammonia and elevated total serum carnitine. CPT1A enzyme activity on the cultured skin cells from affected individuals is 1-5% of normal. Molecular genetic testing is available to confirm the diagnosis if the enzyme test is abnormal. Some state newborn screening programs perform screening for CPT1A deficiency by measuring the ratio of free to total carnitine in blood plasma or serum. Carrier testing for relatives is available using CPT1A enzyme testing or molecular genetic testing.
Prevention of hypoglycemia is recommended to reduce the risk of neurological effects. This can be accomplished with a high carbohydrate, low fat diet and frequent feeding. If acute hypoglycemia occurs, intravenous dextrose should be provided. Individuals with CPT1A deficiency should have regular liver function testing performed. Female carriers of an abnormal CPT1A gene should be informed about the possibility of obstetric complications.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
nformation on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
Research on inborn errors of metabolism is ongoing. Scientists are studying the causes of these disorders and trying to design enzyme replacement therapies that will return a missing enzyme to the body.
Fauci AS, Braunwald E, Isselbacher KJ, et al. Eds. Harrison’s Principles of Internal Medicine. 14th ed.McGraw-Hill Companies. New York, NY; 1998:2479.
Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:2305, 2317-18.
Adams RD, Victor M, Ropper AA. Eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:1438-39.
Lyon G, Adams RD, Kolodny EH. Eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. McGraw-Hill Companies. New York, NY; 1996:27,28,101.
McGarry JD. Travels between carnitine palmitoyltransferase I: from liver cell to germ cell with stops in between. Biochem Soc Trans. 2001;20 (Pt2):241-45.
Vockley J, Rinaldo P, Bennett MJ, et al. Synergistic heterozygosity: disease resulting from multi[ple partial defects in one or more metabolic pathways. Mol Genet Metab. 2000;71:10-18.
Bonnefont JP, Demaugre F, Prip-Buus C, et al. Carnitine palmitoyltransferase deficiencies. Mol Genet Metab. 1999;68:424-40.
Tein I. Neonatal metabolic myopathies. Semin Perinatol. 1999;23:125-51.
Morillas M, Lopez-Vinas E, Valencia A, et al. Structural model of carnitine palmitoyltransferase I based on the carnitine-acetyltransferase crystal. Biochem J. 2004;379(Pt3):777-84.
Gobin S, Thuillier L, Jogl G, et al. Functional and structural basis of carnitine palmitoyltransferase 1A deficiency. J Biol Chem. 2003;278:50428-434.
Shigematsu Y, Hirano S, Hata I, et al. Selective screening for fatty acid oxidation disorders by tandem mass spectrometry: difficulties in practical discrimination. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;15:63-72.
Gobin S, Bonnefont JP, Prip-Buus C, et al. Organization of the human liver carnitine palmitoyltransferase 1 gene (CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia. Hum Genet. 2002;111:179-89.
Invernizzi F, Burlin AB, Donadio A, et al. Lethal neonatal presentation of carnitine palmitoyltransferase I deficiency. J Inherit Metab Dis. 2001;24:601-02.
FROM THE INTERNET
Bennett, MJ and Narayan SB, (Posted 7/27/05). Carnitine Palmitoyltransferase 1A Deficiency. In GeneReviews at Genetests:Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2006. Available at http://genetests.org. Accessed 3/06.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Carnitine Palmitoyltransferase I Deficiency. Number; 255120: Last Edit Date; 8/23/2004.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Carnitine Palmitoyltransferase I, Muscle; CPT1B Entry Number; 601987: Last Edit Date; 8/6/2002.
Vladutiu GD. Mind Over Matter: The Realities of a Common Muscle Disease. ©1999-2004 FOD Support Family Support Group. 4pp.
Vladutiu GD. Fundamental differences [between CPT-I and CPT-II]. ©1999-2000. The Spiral Notebook. 2pp.
Roe CR. Diagnostic Approach to Disorders of Fat Oxidation/Information for Clinicians. ©1999-2004 FOD Support Family Support Group. 11pp.
Bonnefort J-P, Thullier L. Carnitine palmitoyltransferase 1 deficiency. Orphanet. April 2002. 2pp.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100