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Carnitine Deficiency (carnitine + deficiency)
Selected AbstractsVitamin and trace metal levels in recessive dystrophic epidermolysis bullosaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2004S Ingen-Housz-Oro ABSTRACT Background, In recessive dystrophic epidermolysis bullosa (RDEB), a good nutritional balance is necessary to obtain healing of the chronic wounds. However, involvement of the oral mucosa and oesophagus stenosis may be responsible for severe nutritional deficiencies. Objective, In order to propose an adapted nutritional management, we studied the vitamin and trace metal status of 14 RDEB patients. Methods, Height and weight were measured. Plasma levels of albumin, iron, ferritin, calcium, parathyroid hormone (PTH), folates, vitamins C, D, B12, A, E, B1, B6, PP and B2, zinc, selenium, carnitine and copper were measured. Results, Most patients had a significant growth retardation. We found iron, vitamin D, C, B6, PP, zinc and selenium deficiencies in 36,70% of the patients, without clinical expression, except in one case. Vitamin B1, 12, B2, A/RBP, E/lipids and carnitine were normal. The three patients with gastrostomy feeding had better growth but still a protein deficiency and sometimes vitamin C, B6, PP, zinc and carnitine deficiencies. Conclusion, Vitamin and trace metal deficiencies are frequent in RDEB, even in patients receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood. [source] Interaction between Anticonvulsants and Human Placental Carnitine TransporterEPILEPSIA, Issue 3 2004Shu-Pei Wu Summary: Purpose: To examine the inhibitory effect of anticonvulsants (AEDs) on carnitine transport by the human placental carnitine transporter. Methods: Uptake of radiolabeled carnitine by human placental brush-border membrane vesicles was measured in the absence and presence of tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), valproic acid (VPA), and phenytoin (PHT). The mechanism of the inhibitory action of TGB was determined. Results: Most of the AEDs inhibited placental carnitine transport. Kinetic analyses showed that TGB had the greatest inhibitory effect [50% inhibitory concentration (IC50, 190 ,M)], and the order of inhibitory potency was TGB > PHT > GBP > VPA > VGB, TPM > LTG. Further studies showed that TGB competitively inhibited carnitine uptake by the human placental carnitine transporter, suggesting that it may be a substrate for this carrier. Conclusions: Although the involvement of carnitine deficiency in fetal anticonvulsant syndrome requires further evaluation, potential interference with placental carnitine transport by several AEDs was demonstrated. Despite the higher inhibitory potency of TGB, given the therapeutic unbound concentrations, the results for VPA and PHT are probably more clinically significant. [source] Development and characterization of an animal model of carnitine deficiencyFEBS JOURNAL, Issue 6 2001Markus Spaniol Mammals cover their carnitine needs by diet and biosynthesis. The last step of carnitine biosynthesis is the conversion of butyrobetaine to carnitine by butyrobetaine hydroxylase. We investigated the effect of N -trimethyl-hydrazine-3-propionate (THP), a butyrobetaine analogue, on butyrobetaine hydroxylase kinetics, and carnitine biosynthesis and body homeostasis in rats fed a casein-based or a vegetarian diet. The Km of butyrobetaine hydroxylase purified from rat liver was 41 ± 9 µmol·L,1 for butyrobetaine and 37 ± 5 µmol·L,1 for THP, and THP was a competitive inhibitor of butyrobetaine hydroxylase (Ki 16 ± 2 µmol·L,1). In rats fed a vegetarian diet, renal excretion of total carnitine was increased by THP (20 mg·100 g,1·day,1 for three weeks), averaging 96 ± 36 and 5.3 ± 1.2 µmol·day,1 in THP-treated and control rats, respectively. After three weeks of treatment, the total carnitine plasma concentration (8.8 ± 2.1 versus 52.8 ± 11.4 µmol·L,1) and tissue levels were decreased in THP-treated rats (liver 0.19 ± 0.03 versus 0.59 ± 0.08 and muscle 0.24 ± 0.04 versus 1.07 ± 0.13 µmol·g,1). Carnitine biosynthesis was blocked in THP-treated rats (,0.22 ± 0.13 versus 0.57 ± 0.21 µmol·100 g,1·day,1). Similar results were obtained in rats treated with the casein-based diet. THP inhibited carnitine transport by rat renal brush-border membrane vesicles competitively (Ki 41 ± 3 µmol·L,1). Palmitate metabolism in vivo was impaired in THP-treated rats and the livers showed mixed steatosis. Steady-state mRNA levels of the carnitine transporter rat OCTN2 were increased in THP-treated rats in skeletal muscle and small intestine. In conclusion, THP inhibits butyrobetaine hydroxylase competitively, blocks carnitine biosynthesis in vivo and interacts competitively with renal carnitine reabsorption. THP-treated rats develop systemic carnitine deficiency over three weeks and can therefore serve as an animal model for human carnitine deficiency. [source] Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency,HUMAN MUTATION, Issue 8 2010Fang-Yuan Li Abstract Systemic primary carnitine deficiency (CDSP) is caused by recessive mutations in the SLC22A5 (OCTN2) gene encoding the plasmalemmal carnitine transporter and characterized by hypoketotic hypoglycemia, and skeletal and cardiac myopathy. The entire coding regions of the OCTN2 gene were sequenced in 143 unrelated subjects suspected of having CDSP. In 70 unrelated infants evaluated because of abnormal newborn screening (NBS) results, 48 were found to have at least 1 mutation/unclassified missense variant. Twenty-eight of 33 mothers whose infants had abnormal NBS results were found to carry at least 1 mutation/unclassified missense variant, including 11 asymptomatic mothers who had 2 mutations. Therefore, sequencing of the OCTN2 gene is recommended for infants with abnormal NBS results and for their mothers. Conversely, 52 unrelated subjects were tested due to clinical indications other than abnormal NBS and only 14 of them were found to have at least one mutation/unclassified variant. Custom designed oligonucleotide array CGH analysis revealed a heterozygous ,1.6 Mb deletion encompassing the entire OCTN2 gene in one subject who was apparently homozygous for the c.680G>A (p.R227H) mutation. Thus, copy number abnormalities at the OCTN2 locus should be considered if by sequencing, an apparently homozygous mutation or only one mutant allele is identified. ©2010 Wiley-Liss, Inc. [source] Effect of ,-butyrobetaine on fatty liver in juvenile visceral steatosis miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2001Yasuhiko Higashi We pharmacokinetically examined the effect of ,-butyrobetaine, a precursor of l -carnitine, on the change of fatty acid metabolism in juvenile visceral steatosis (JVS) mice, which have systemic l -carnitine deficiency due to lack of l -carnitine transporter activity. The concentrations of total free fatty acid (FFA), palmitic acid and stearic acid in the liver of JVS mice were significantly higher than those in wild-type mice. After intravenous administration of ,-butyrobetaine (50 mg kg,1), the concentration of l -carnitine in the plasma of JVS mice reached about twice that of the control level and levels in the brain, liver and kidney were also significantly increased, whereas those in wild-type mice hardly changed. Although the plasma concentrations of FFA in both types of mice were unchanged after administration of ,-butyrobetaine, the concentrations of palmitic acid and stearic acid were significantly decreased. In particular, the liver concentration of FFA in JVS mice was decreased to the wild-type control level, accompanied by significant decreases in long-chain fatty acids, palmitic acid and stearic acid, whereas those in wild-type mice were not changed. These results suggest that ,-butyrobetaine can be taken up into organs, including the liver, of JVS mice, and transformed to l -carnitine. Consequently, administration of ,-butyrobetaine may be more useful than that of l -carnitine itself for treatment of primary deficiency of carnitine due to a functional defect of the carnitine transporter. [source] Disorders of carnitine transport and the carnitine cycle,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2006Nicola Longo Abstract Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2, CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine deficiency, characterized by increased losses of carnitine in the urine and decreased carnitine accumulation in tissues. Patients can present with hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac myopathy. This disease responds to carnitine supplementation. Defects in the liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic hypoglycemia. The heart and the muscle, which express a genetically distinct form of CPT1, are usually unaffected. These patients can have elevated levels of plasma carnitine. CACT deficiency presents in most cases in the neonatal period with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2 present more frequently in adults with rhabdomyolysis triggered by prolonged exercise. More severe variants of CPT2 deficiency present in the neonatal period similarly to CACT deficiency associated or not with multiple congenital anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat diet supplemented with medium chain triglycerides that can be metabolized by mitochondria independently from carnitine, carnitine supplements, and avoidance of fasting and sustained exercise. © 2006 Wiley-Liss, Inc. [source] Lipid resuscitation in a carnitine deficient child following intravascular migration of an epidural catheter,ANAESTHESIA, Issue 2 2010G. K. Wong Summary A child with cerebral palsy and carnitine deficiency developed ventricular arrhythmias with loss of cardiac output during elective surgery under general anaesthesia with concomitant epidural analgesia. Sinus rhythm was restored on administration of adrenaline, but hypotension persisted despite resuscitation. Bolus administration of 0.8 ml.kg,1 (20 ml) lipid emulsion resulted in rapid improvement in cardiac output. Blood samples taken before and after the lipid bolus did not demonstrate toxic concentrations of bupivacaine. This case suggests that carnitine deficiency may increase susceptibility to bupivacaine cardiotoxicity. [source] | |||||||||||||