Carnitine transporter deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Hypoketotic hypoglycemia, seizures, vomiting, lethargy progressive to coma; cardiomyopathy; chronic muscle weakness; carnitine deficiency in plasma and muscle, and increased excretion of free carnitine in urine; defective transport of carnitine into cultured fibroblasts and mutations in the SLC22A5 gene which codes for the sodium ion-dependent carnitine transporter organic cation transporter. The inborn errors of fatty acid oxidation, including carnitine transporter deficiency, represent a relatively recently recognized area of human disease. The rate of discovery of distinct disorders has increased rapidly since the discovery of medium-chain acyl CoA dehydrogenase deficiency in 1982. The classic, and frequently the initial presentation of carnitine transporter deficiency, is hypoketotic hypoglycemia, as in most disorders of fatty acid oxidation. Clinical chemistry in the acute hypoketotic episode is also consistent with Reye syndrome, with hyperammonemia and increased levels of transaminases.
Carnitine-acylcarnitine translocase deficiency
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Carnitine translocase (carnitine:acylcarnitine carrier) deficiency is a recently discovered disorder of fatty acid oxidation. First described in 1992, the disease accounted for ten of 107 patients in the Saudubray experience with abnormalities in the oxidation of fatty acids. Many patients have developed symptoms and died in infancy. Mitochondrial oxidation of long-chain fatty acids provides an important source of energy for the heart, as well as for skeletal muscle during prolonged aerobic work and for hepatic ketogenesis during long-term fasting. The carnitine shuttle is responsible for transferring long-chain fatty acids across the barrier of the inner mitochondrial membrane to gain access to the enzymes of ß-oxidation. Episodes typically follow prolonged fasting, which is a common response of infants to intercurrent infectious disease.
Carnitine palmitoyl transferase I deficiency
William Nyhan, Georg Hoffmann, Bruce Barshop, Aida Al-Aqeel in Atlas of Inherited Metabolic Diseases 3E, 2012
Deficiency of carnitine palmitoyl transferase (CPT) I was first described in 1980 by Bougneres et al. [1, 2], in a patient who developed hypoketotic hypoglycemia and morning seizures at eight months of age. They referred to the disorder as deficiency of hepatic carnitine acyl transferase, or palmitoyl transferase, to distinguish it from the deficiency of muscular CPT, in which there is a very different phenotype of muscle pain and rhabdomyolysis, usually observed in adults after exercise [3]. They documented deficient carnitine acyl transferase activity in biopsied liver. Bonnefont et al. [4] clearly distinguished Figure 35.1 The transport of long-chain fatty acids into the mitochondrial sites of b-oxidation involves first the formation of acylcarnitine esters, catalyzed by carnitine palmitoyl transferase (CPT) I; once inside the membranes the liberation of fatty acyl CoA is catalyzed by CPT II. CPT I and II, carnitine palmitoyl transferase I and II; CoASH, coenzyme A; R, fatty acyl side chain.
Carnitine is associated with fatigue following chemoradiotherapy for head and neck cancer
Published in Acta Oto-Laryngologica, 2015
Kazuhira Endo, Akira Tsuji, Satoru Kondo, Naohiro Wakisaka, Shigeyuki Murono, Tomokazu Yoshizaki
Conclusion: Longitudinal assessments of carnitine and fatigue in patients with head and neck squamous cell carcinoma suggest that cisplatin damages the carnitine system in patients undergoing chemoradiotherapy and that carnitine deficiency increases fatigue. Objectives: The purpose of this study was to monitor carnitine levels and fatigue in patients who received cisplatin-based CRT and, for comparison, in patients treated by surgery alone. Methods: To investigate the level of carnitine, mice were administered cisplatin. Next, a prospective analysis was performed to compare plasma carnitine levels before and after cisplatin-based chemoradiotherapy and to assess the relationship between carnitine levels and fatigue. Results: The plasma levels of total carnitine (TC), free carnitine (FC), and fatty acylcarnitine (AC) were significantly lower in mice receiving cisplatin compared with control mice. Mean total carnitine and free carnitine levels were significantly lower 2 weeks after chemoradiotherapy (total carnitine: Mean = 45.6, SD = 16.5, p = 0.01; free carnitine: Mean = 37.8, SD = 12.7, p = 0.02) than before chemoradiotherapy (total carnitine: Mean = 57.7, SD = 12.2; free carnitine: Mean = 48.1, SD = 11.6). There was a significant inverse correlation between carnitine levels and fatigue after chemoradiotherapy.
Carnitine as an essential nutrient.
Published in Journal of the American College of Nutrition, 1986
Carnitine performs a critically important role in energy metabolism and is synthesized in the healthy adult predominantly in the liver and kidney. The typical well balanced American diet contains significant amounts of carnitine as well as the essential amino acids and micronutrients needed for carnitine biosynthesis. Thus carnitine is an infrequent problem in the healthy, well nourished adult population in the United States. However, carnitine can be a conditionally essential nutrient for several different types of individuals. Preterm infants require carnitine for life-sustaining metabolic processes but have a carnitine biosynthetic capability that is not fully developed. There is an increasing number of documented problems with carnitine metabolism in preterm infants not receiving an exogenous source of carnitine indicating that endogenous biosynthesis of carnitine is not adequate to meet the infant's need. Children with different forms of organic aciduria appear to have a greatly increased need for carnitine to function in the excretion of the accumulating organic acids. This need exceeds their dietary carnitine intake and carnitine biosynthetic capability. Renal patients treated with chronic hemodialysis appear to lose carnitine via the hemodialysis treatment, and this loss cannot be repleted simply by endogenous biosynthesis and dietary intake. Treatment with drugs such as valproic acid and metabolic stresses such as trauma, sepsis, organ failure, etc, can also result in a requirement for exogenous carnitine. Accurate assessment of the carnitine status of patients at risk for carnitine deficiency is fundamental to the identification of those patients who require carnitine as the result of altered metabolism.
Effects of l-carnitine and niacin supplied by drinking water on fattening performance, carcass quality and plasma l-carnitine concentration of broiler chicks
Published in Archives of Animal Nutrition, 2003
L. Çelik, Ö Öztürkcan, T. C. İnal, N. Canacankatan, L. Kayrin
The present study was initiated to determine whether dietary supplemental L-carnitine and niacin affect growth performance, carcass yield, abdominal fat and plasma L-carnitine concentration of broiler chicks. One-day-old broiler chicks (COB500) were used in the experiment. A two by two factorial arrangement was employed with two levels (0 and 50 mg/l) of supplemental L-carnitine and two levels (0 or 50 mg/l) of supplemental niacin in drinking water as main effects. Body weight gain was significantly improved by L-carnitine, or L-carnitine + niacin supplementation during the first 3 weeks. However, supplemental L-carnitine and niacin did not change body weight gain during the last 3 weeks of the experimental period. Supplemental L-carnitine significantly improved feed intake during the first 3 weeks. Supplemental L-carnitine or niacin did not influence carcass weight, carcass yield and abdominal fat weight. L-carnitine content in the plasma was significantly higher in the groups receiving supplemental L-carnitine and L-carnitine + niacin. It is concluded that dietary supplemental L-carnitine or L-carnitine + niacin could have positive effects on body weight gain and feed intake during the early stages of growing. However, supplemental L-carnitine or L-carnitine + niacin were not of benefit regarding the complete growth period.