Background Carnitine Palmitoyl Transferase II (CPT II) Deficiency is a disorder of mitochondrial fatty acid oxidation. Fatty acid oxidation normally generates ATP inside the mitochondria and provides acetyl-CoA for gluconeogenesis. Long-chain fatty acids require carnitine for transport into the mitochondria as long-chain acyl-carnitine esters (i.e. carnitine esterified to a fatty acid). CPT II is located on the inner mitochondrial membrane and acts to convert long-chain acyl-carnitine substrates that are transported across the outer mitochondrial membrane to acyl-CoAs for subsequent ß-oxidation. Deficiency of CPT II results in the accumulation of long-chain acylcarnitines inside the mitochondria and in the plasma. Medium- and short-chain (C8 and shorter) fatty acids do not require CPT II and are metabolized normally. Muscle is particularly dependent on fatty acid oxidation for energy production. Clinical There are three clinical presentations of CPT II Deficiency. The classic form has adult onset of exercise-induced muscle weakness, often with rhabdomyolysis and myoglobinuria that can be associated with acute renal failure. CK levels are found to be elevated only during a symptomatic period. Carnitine levels are normal. A second phenotype is often fatal in the period from 3 to 18 months of age. Presentation can be onset of seizures with hepatomegaly, non-ketotic hypoglycemia, cardiomyopathy, hypotonia, and muscle weakness. Plasma free carnitine levels are low and acyl-carnitine high. A severe form presents in the newborn period with non-ketotic hypoglycemia, cardiomyopathy, muscle weakness, and renal dysgenesis in some patients. All of these patients have expired within days of birth. These different clinical presentations appear to be correlated with residual CPT II enzyme activity. Adult onset patients are found to have approximately 25% of normal activity while the other clinical groups have less than 15%. Testing Newborn screening of a dried blood spot using tandem mass spectrometry detects elevations of several long-chain acylcarnitines (i.e. C16, C18, C18:1 and C18:2). These findings are characteristic but not definitive of CPT II Deficiency, because Carnitine/ Acylcarnitine Translocase Deficiency has similar findings. Quantitative urine organic acid determination is usually not helpful, as elevations of long chain fatty acids, including dicarboxylic and 3-hydroxy-dicarboxylic acids, are not always present. Plasma acylcarnitine profile results confirm the findings on a dried blood spot. Definitive testing is performed by direct enzyme testing in fibroblasts, leukocytes, liver, or muscle biopsy. Treatment CPT II deficiency varies with the clinical type. Patients with adult-onset muscle form of the disease must alter their lifestyle and refrain from rigorous exercise. It is probably prudent to avoid prolonged fasting. Medium-chain triglyceride oil may be beneficial for all patients, because it bypasses the need for CPT II activity. Aggressive treatment of acutely ill infants with IV glucose and cardiac support is critical. L-Carnitine supplementation should be instituted. Any intercurrent infection or illness will be life threatening to patients affected with the childhood form. Because the diagnosis and therapy of CPT II Deficiency is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician. Inheritance This disorder most often follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder. As with all genetic diseases, genetic counseling may be appropriate to help families understand recurrence risks and ensure that they receive proper evaluation and care.
References Demaugre, F., Bonnefont, J-P., Colonna, M., et al. Infantile form of Carnitine palmitoyltransferase II deficiency with hepatomuscular symptoms and sudden death. Physiopathological approach to Carnitine palmitoyltransferase II deficiency. J Clin Invest 87:859, 1991. Hug, G., Bove, K.E. and Soukup, S. Lethal neonatal multiorgan deficiency of Carnitine palmitoyltransferase II. N Engl J Med 325:1862, 1991. Roe, C.R. and Ding, J. Mitochondrial Fatty Acid Oxidation Disorders. In, The Metabolic and Molecular Basis of Inherited Disease. 8th Edition, 2001. Scriver, Beaudet, et al. McGraw-Hill. Chapter 101, pg. 2297-2326. Zinn, A.B., Zurcher, V.L., Kraus, F., et al. Carnitine palmitoyltransferase B (CPT B) deficiency: a heritable cause of neonatal cardiomyopathy and dysgenesis of the kidney. Pediatr Res 29:73A, 1991. Web Sites SaveBabies.org
Site established and maintained by parents of newborns affected with a rare genetic defect, with information for parents and professionals and links to other informative sites. National Newborn Screening and Genetics Resource Center
Provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.
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The analyses conducted by PerkinElmer Genetics produce results that can be used by qualified physicians in the diagnosis of disorders described herein. Evidence of these conditions will be detected in the vast majority of affected individuals; however, due to genetic variability, age of the patient at the time of specimen collection, quality of the specimen, health status of the patient, and other variables, such conditions may not be detected in all affected patients. PerkinElmer Genetics makes no warranty whatsoever, express or implied, including any warranty as to accuracy, completeness or timeliness, concerning the information contained herein, and you should not assume that such information is complete or the most up-to-date information available. PerkinElmer Genetics shall not be liable for any loss, claim or damages caused in whole or in part by our provision of, or your use of, any of the information contained herein. As a general statement, this information was drawn from published literature and is not drawn from our patient population or screening experience. The information contained herein is not intended to be a substitute for professional medical advice and should not be used for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions.
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