Secondary Carnitine Deficiency Research Articles

A Rare Case Report of Hypoketotic Hypoglycemia Induced Seizures Due to Secondary Carnitine Deficiency In a 44-year-old Female

A Rare Case Report of Hypoketotic Hypoglycemia Induced Seizures Due to Secondary Carnitine Deficiency In a 44-year-old Female

Secondary Carnitine Deficiency in Neonates and Infants Requiring Surgery for Intestinal Obstructions-An Underestimated and Undermanaged Problem.

This study aims to elucidate the relationship between intestinal obstruction and carnitine deficiency in neonates and infants. We retrospectively reviewed medical records of 330 neonates and infants, younger than six months, who underwent surgery for intestinal obstruction at our institute from January 2009 to April 2022. The analysis focused on clinical symptoms, related signs, complications, and etiology of the intestinal obstruction. Tandem mass spectrometry (MS/MS) or urine organic acid analysis was conducted for 47 patients, revealing carnitine deficiency in 16 patients. The incidence of carnitine deficiency was 34.0% in the suspicious group and 4.8% overall, significantly higher than in the general population in Taiwan. Notably, patients with carnitine deficiency experienced prolonged ileus, with a mean fasting duration of 41.7 days (range 7.8-65.5 days), compared to 10.8 days (range 8.2-13.4 days) in patients without carnitine deficiency. Carnitine replacement therapy was administered to twelve patients at dosages ranging from 32 to 90 mg/kg/day. One patient exhibited a drug allergy with skin rashes. Our findings suggest that carnitine deficiency should be considered in cases of neonatal and infant intestinal obstruction. Replacement therapy is straightforward and can be prognostically beneficial for some patients. Therefore, we recommend generalizing MS/MS and urine organic acid analysis, particularly for patients with prolonged ileus.

Free carnitine concentrations and biochemical parameters in medium-chain acyl-CoA dehydrogenase deficiency: Genotype-phenotype correlation.

Biallelic variants in the ACADM gene cause medium-chain acyl-CoA dehydrogenase deficiency (MCADD). This study reports on differences in the occurrence of secondary free carnitine (C0) deficiency and different biochemical phenotypes related to genotype and age in 109 MCADD patients followed-up at a single tertiary care center during 22 years. C0 deficiency occurred earlier and more frequently in c.985A>G homozygotes (genotype A) compared to c.985A>G compound heterozygotes (genotype B) and individuals carrying variants other than c.985A>G and c.199C>T (genotype D) (median age 4.2 vs. 6.6 years; p < 0.001). No patient carrying c.199C>T (genotype C) developed C0 deficiency. A daily dosage of 20-40 mg/kg carnitine was sufficient to maintain normal C0 concentrations. Compared to genotype A as reference group, octanoylcarnitine (C8) was significantly lower in genotypes B and C, whereas C0 was significantly higher by 8.28 μmol/L in genotype C (p < 0.05). In conclusion, C0 deficiency is mainly found in patients with pathogenic genotypes associated with high concentrations of presumably toxic acylcarnitines, while individuals carrying the variant c.199C>T are spared and show consistently mild biochemical phenotypes into adulthood. Low-dose carnitine supplementation maintains normal C0 concentrations. However, future studies need to evaluate clinical benefits on acute and chronic manifestations of MCADD.

Newborn screening for 3-methylcrotonyl-CoA carboxylase deficiency in Zhejiang province, China.

3-Methylcrotonyl-CoA carboxylase deficiency (3-MCCD) is an autosomal recessive inborn defect of leucine catabolism caused by MCCC1 or MCCC2 variants. 3-MCCD is considered to be a relatively benign disorder with favorable outcome. We report the biochemical, clinical, and molecular features of patients with 3-MCCD. From January 2009 to August 2022, 4,402,587 newborns were screened by tandem mass spectrometry. Newborns with increased C5OH concentrations were recalled for repeated testing, urine organic acid analysis and molecular genetic analysis were performed if the second test was still positive. A total of 53 patients were diagnosed with 3-MCCD. The estimated incidence of 3-MCCD in Zhejiang Province was 1 in 83,068 newborns. All these 53 patients exhibited increased C5OH concentrations in blood. 94% (50/53) of the patients had markedly increased urinary 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. All these 53 patients did not present any clinical symptom. Twenty-three of 53 patients had secondary carnitine deficiency. Twenty-eight patients had variants in MCCC1 and 25 had variants in MCCC2. Eleven novel variants were found in MCCC1 and MCCC2. The c.639+2T>A and c.1144-1147delinsTTTT were the most common variant in MCCC1 and MCCC2 gene, respectively. We elucidated the incidence of 3-MCCD in Zhejiang province, China. All patients showed asymptomatic and present normal growth and development during follow-up. Eleven novel MCCC1 and MCCC2 variants were identified, which expanded the variant spectrum.

Carnitine Supplementation Ameliorates the Steatosis and Ketosis Induced by Pivalate in Rats

These studies examined the effect in rats of carnitine supplementation on variables of fat metabolism altered by administration of sodium pivalate, a compound which induces a carnitine deficiency. Weanling male rats received 20 mmol/L sodium pivalate or 20 mmol/L sodium bicarbonate in their drinking water for 2 wk. They were food-deprived for 24 h, and to maximize fatty acid oxidation, were cold-stressed for 4 h. In Experiment 1, group 1 received the bicarbonate, group 2 received the pivalate, group 3 received the pivalate and 0.46 mmol L-carnitine in the diet/d, while group 4 received the pivalate and 0.95 mmol L-carnitine in the diet/d. In Experiment 2, group 1 received unsupplemented drinking water, group 2 received the bicarbonate, group 3 received the pivalate, and group 4 received the pivalate and 0.95 mmol L-carnitine in the diet/d. Pivalate-treated rats given the low carnitine diet had plasma and liver triglyceride levels (Experiment 1), plasma β-hydroxybutyrate concentrations (Experiments 1 and 2) and urinary dicarboxylic acid excretion (Experiment 2) significantly greater than those of controls (P < 0.05). The reduced tissue carnitine concentrations, starvation ketosis and lipid accumulation in the liver are findings also reported for human secondary carnitine deficiency due to organic acidurias. Supplementing the diet with L-carnitine at the level of 0.95 mmol/d significantly raised plasma and tissue carnitine concentrations and reduced the plasma β-hydroxybutyrate and liver triglyceride concentrations to levels not significantly different than control values. Carnitine supplementation ameliorates the degree of liver lipid accumulation and exaggerated starvation ketosis induced by pivalate.

β-Hydroxybutyrate Oxidation Is Reduced and Hepatic Balance of Ketone Bodies and Free Fatty Acids Is Unaltered in Carnitine-Depleted, Pivalate-Treated Rats

These experiments were designed to determine whether carnitine depletion in the rat due to pivalate administration causes reduced β-hydroxybutyrate oxidation and alterations in hepatic balance of ketone bodies and free fatty acids, relative to control rats. Male rats were given 20 mmol/L sodium pivalate for 2 wk to induce a secondary carnitine deficiency. Control animals were given 20 mmol/L sodium bicarbonate in their drinking water. In the ketone utilization experiment, rats were food-deprived for 24 h and infused with the sodium salt of β-hydroxybutyrate to maintain total plasma ketone concentrations between 6.0 and 10.0 mmol/L. After a bolus of 3-hydroxy[3-14C]butyrate, the recovery of expired 14CO2 collected during the ensuing 100 main was significantly lower in the pivalate-treated rats than in the controls (P < 0.05). In the second experiment, blood samples from pivalate-treated and control rats were collected from the abdominal aorta, portal vein and hepatic vein to determine the hepatic balance (hepatic input — hepatic output) of ketone bodies and free fatty acids. No significant differences were seen between the two treatment groups for either ketone bodies or free fatty acids. We conclude that the higher plasma ketone concentrations seen in food-deprived, pivalate-treated rats were due to a lower rate of ketone utilization. No evidence of pivalate influence upon ketone production was found.

311: SEVERE HYPERAMMONEMIA CAUSED BY CARNITINE DEFICIENCY DURING ADULTHOOD

Introduction: Carnitine is a necessary co-factor in the oxidation of fatty acids as part of the urea cycle; deficiency of which may lead to heart or liver failure. Primary carnitine deficiency due to transporter defects or mutations is seen in infants. Secondary carnitine deficiency is the result of whole-body carnitine deficiency. Here, we discuss a case of secondary deficiency due to vegetarianism, leading to severe hyperammonemia. Description: A 23-year-old woman was admitted with one day of vomiting and diarrhea. On arrival, she was confused but alert, though rapidly decompensated and developed obtundation, clonus, rigidity, posturing, and non-reactive mydriatic pupils, requiring emergent intubation. Work-up was significant for elevated ammonia to 581 umol/L with CT head showing severe brain edema prompting placement of external ventricular drain for intracranial hypertension and frequent hypertonic saline administration. Given significant hyperammonemia with otherwise negative work-up, the patient’s presentation was concerning for a urea cycle defect. The patient was dialyzed and started on arginine, sodium benzoate/phenylacetate, citrulline, and buphenyl. Further history revealed a diet devoid of meat. Plasma amino acid analysis revealed decreased total carnitine 3 umol/L (27-73) and free carnitine 2 umol/L (20-55). There were no mutations in the carnitine transport gene or deficient enzymatic activity for the urea cycle. After one week, she was awake, alert, and was extubated shortly thereafter. Once tolerating oral intake, her diet of was supplemented with oral carnitine. She was able to make a full recovery and return home without deficits from baseline prior to admission. Discussion: Common causes of hyperammonemia are hepatic failure, genetic urea cycle defects, and organic academies, which were ruled out in this case. Carnitine is an important co-factor in the metabolism of long-chain fatty acids and its disruption impairs ammonia excretion through inhibition of the urea cycle. Secondary carnitine deficiency is seen in severe malnutrition, and causes hyperammonemia and encephalopathy. This case is particularly important to note, as fatty acid oxidation disorders based on pure dietary deficiency that presents during adulthood are uncommon and not frequently considered in the differentials.

Evaluation of plasma carnitine status in patients diagnosed with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and manifests mainly as autoinflammation of the joints and other tissues. Several treatment options such as nonsteroidal antiinflammatory drugs, methotrexate, and intra-articular steroids are widely used to relieve and improve this inflammation. Secondary carnitine deficiency can be detected in chronic diseases by either renal loss or increased demand. While carnitine status can be associated with several conditions, in the present study our aim is to determine the levels of free carnitine and acyl-carnitine in Turkish JIA patients. One hundred and fourteen patients diagnosed with juvenile idiopathic arthritis and 50 healthy individuals who served as the control group were included in the study. A fasting blood sample was collected from the children in both groups to determine free carnitine and acylcarnitine ester by quadripole electrospray tandem mass spectrometry (ESI-MS/ MS). Screening of acyl-carnitine profile revealed free carnitine, C14, C14:2, C16, C16-OH, and C18 carnitine levels were higher (p < 0.0001, p < 0.0001, p < 0.001, p < 0.001, and p = 0.011, respectively), while C2, C3, C4, C6, C8, C10, C10:1, C10:2, C3DC, C4DC, C5DC, C4-OH, and C18:1-OH carnitine levels were lower (p < 0.0001) in JIA patients in comparison to the control group. Total acyl-carnitine levels (p < 0.001) and acyl-carnitine to free carnitine ratio (p < 0.001) were also lower in JIA patients than the control group. Free carnitine levels were significantly higher (48.05 ± 13.36 μmol/L) in patients under antiinflammatory drug therapy than those who did not receive any treatment (43.18 ± 7.96 μmol/L) (p = 0.004). In the present study we were not able to define secondary carnitine deficiency in JIA patients, although free carnitine and acyl-carnitine variations were detected in JIA patients. In conclusion, routine carnitine supplementation is not recommended in all patients with JIA.

Carnitine deficiency among hospitalized pediatric patients: A retrospective study of critically ill patients receiving extracorporeal membrane oxygenation therapy.

BackgroundThe metabolic demands associated with critical illness place patients at risk for nutrition deficits. Carnitine is a small molecule essential for fatty acid oxidation and gluconeogenesis. Secondary carnitine deficiency can have clinically significant complications and has been observed anecdotally in patients receiving extracorporeal membrane oxygenation (ECMO) therapy at our institution. Guidelines for monitoring and supplementing carnitine are lacking. This retrospective study determined whether critically ill pediatric patients receiving ECMO have an increased risk of carnitine deficiency.MethodsAcylcarnitine analysis was performed on residual specimens from patients who received ECMO therapy. The control data were a convenience sample gathered by chart review of patients who had been tested for carnitine during a hospitalization.ResultsAcylcarnitines were measured in 217 non‐ECMO patients and 81 ECMO patients. Carnitine deficiency, based on age‐specific reference ranges, was observed in 41% of ECMO cases compared with 21% of non‐ECMO cases. Multivariable analysis of age‐matched patients identified that the odds of carnitine deficiency were significantly lower among patients on the floor compared with ECMO patients (odds ratio, 0.21; 95% CI, 0.10–0.44). Age‐specific frequency of qualitative carnitine deficiency ranged from 15% (patients >5 years old) to 56% (patients 1 week to 1 month old) in ECMO patients and 15% (patients >5 years old) to 34% (patients 1–5 years old) in non‐ECMO patients.ConclusionIn this study, ECMO patients were carnitine deficient more frequently compared with other inpatients, with the highest rates of deficiency among ECMO patients between 1 week and 1 month old.

Effectiveness of Propionyl-L-Carnitine Supplementation on Exercise Performance in Intermittent Claudication: A Systematic Review.

Lower extremity peripheral artery disease (PAD) affects 8.5 million people in the United States and more than 200 million worldwide. The most significant risk factors for PAD are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking. Intermittent claudication (IC) is the predominant symptom of PAD, but only about 10% of patients with PAD experience IC and are associated with reduced exercise capacity. The pathophysiology of IC is characterized by different degrees of stenosis and obstruction, with a progressive reduction in distal perfusion pressure and blood flow. Supervised exercise therapy is recommended as the initial therapy for IC, but the recommendations for medical treatment of IC vary significantly. Propionyl L-carnitine is an acyl derivative of levocarnitine (L-carnitine) and is indicated for patients with the peripheral arterial occlusive disease. It corrects secondary muscle carnitine deficiency in patients with PAD, significantly improving the walking capacity; its levels increase in serum and muscle. Thus, it is suggested to enhance blood flow and oxygen supply to the muscle tissue via improved endothelial function, thereby reducing hypoxia-induced cellular and biochemical disruptions.

Limited Impact of Pivalate-Induced Secondary Carnitine Deficiency on Hepatic Transcriptome and Hepatic and Plasma Metabolome in Nursery Pigs.

Administration of pivalate has been demonstrated to be suitable for the induction of secondary carnitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively characterize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of the hepatic transcriptome and hepatic and plasma metabolome of a total of 12 male 5-week-old pigs administered either pivalate (group PIV, n = 6) or vehicle (group CON, n = 6) for 28 days. Pigs of group PIV had approximately 40–60% lower concentrations of free carnitine and acetylcarnitine in plasma, liver and different skeletal muscles than pigs of group CON (p < 0.05). Transcript profiling of the liver revealed 140 differentially expressed genes (DEGs) between group PIV and group CON (fold change > 1.2 or <−1.2, p-value < 0.05). Biological process terms dealing with the innate immune response were found to be enriched with the DEGs (p < 0.05). Using a targeted metabolomics approach for the simultaneous quantification of 630 metabolites, 9 liver metabolites and 18 plasma metabolites were identified to be different between group PIV and group CON (p < 0.05). Considering the limited alterations of the hepatic transcriptome and of the liver and plasma metabolome, it can be concluded that pivalate-induced secondary CD is not associated with significant hepatic metabolism changes in pigs.

Neuroprotective Effects of Carnitine and Its Potential Application to Ameliorate Neurotoxicity.

Carnitine is an essential metabolite that is absorbed from the diet and synthesized in the kidney, liver, and brain. It ferries fatty acids across the mitochondrial membrane to undergo β-oxidation. Carnitine has been studied as a therapy or protective agent for many neurological diseases and neurotoxicity (e.g., prolonged anesthetic exposure-induced developmental neurotoxicity in preclinical models). Preclinical and clinical data support the notion that carnitine or acetyl carnitine may improve a patient's quality of life through increased mitochondrial respiration, release of neurotransmitters, and global gene expression changes, showing the potential of carnitine beyond its approved use to treat primary and secondary carnitine deficiency. In this review, we summarize the beneficial effects of carnitine or acetyl carnitine on the central nervous system, highlighting protective effects against neurotoxicity-induced damage caused by various chemicals and encouraging a thorough evaluation of carnitine use as a therapy for patients suffering from neurotoxicant exposure.

THE IMPORTANCE OF CARNITINE AND ITS METABOLISM IN NEWBORN: LITERATURE REVIEW AND CLINICAL CASE

Aim: To analyze the literature on the processes of formation of endogenous and exogenous carnitine, its metabolism and function in the newborn. Material and methods: The literature data and international clinical recommendations for pathological conditions leading to primary and secondary carnitine deficiency have been retrospectively analyzed. A clinical case of a child with suspected systemic carnitine deficiency is presented. Conclusions: Depending on the reasons that led to carnitine deficiency, there are primary and secondary carnitine deficiency. Primary carnitine deficiency is a rare condition that can lead to metabolic decompensation, muscular and cardiac myopathy, and sudden death. Secondary carnitine deficiency can be caused by a genetically determined congenital metabolic defect, insufficient substrate intake, acquired disorder, immaturity of the biochemical pathway in premature infants, renal failure or iatrogenic exposure. Familiarization with the main causes of carnitine deficiency in newborns will more effectively detect and correct the clinical manifestations of this condition.

Genetic analysis of a child with very long chain acyl-CoA dehydrogenase deficiency

To analyze the clinical and molecular characteristics of a child with very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Peripheral blood sample of the patient was collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out for the proband. Suspected mutations were validated by Sanger sequencing. The patient, a 12-month-old girl, was admitted for diarrhea, vomiting, fever, poor spirit and decreased blood pressure. During the course of the disease, she also manifested hypertrophic cardiomyopathy, cardiogenic shock, elevated myocardial enzyme kinase, fever and metabolic acidosis, and had died after three days due to ventricular tachycardia and respiratory failure. Genetic testing showed that she has carried heterozygous mutations of of the ACADVL gene, namely c.664G>A (exon 8) and c.1056_1057del (exon 10). Blood screening for metabolic genetic diseases showed increased C12, C14, C16, C18, C14:1, C14:2, C16:1, C4/C3 and C8/C3, accompanied with decreased C0, C0/C16 and C8/C10. VLCADD and secondary carnitine deficiency could not be excluded, which was in keeping with the result of genetic testing. The child was diagnosed with VLCADD, which may be attributed to the compound heterozygous c.664G>A and c.1056_1057del variants of the ACADVL gene.

Mass Spectrometric Analysis of L-carnitine and its Esters: Potential Biomarkers of Disturbances in Carnitine Homeostasis.

Purpose: After a golden age of classic carnitine research three decades ago, the spread of mass spectrometry opened new perspectives and a much better understanding of the carnitine system is available nowadays. In the classic period, several human and animal studies were focused on various distinct physiological functions of this molecule and these revealed different aspects of carnitine homeostasis in normal and pathological conditions. Initially, the laboratory analyses were based on the classic or radioenzymatic assays, enabling only the determination of free and total carnitine levels and calculation of total carnitine esters’ amount without any information on the composition of the acyl groups. The introduction of mass spectrometry allowed the measurement of free carnitine along with the specific and sensitive determination of different carnitine esters. Beyond basic research, mass spectrometry study of carnitine esters was introduced into the newborn screening program because of being capable to detect more than 30 metabolic disorders simultaneously. Furthermore, mass spectrometry measurements were performed to investigate different disease states affecting carnitine homeostasis, such as diabetes, chronic renal failure, celiac disease, cardiovascular diseases, autism spectrum disorder or inflammatory bowel diseases.Results: This article will review the recent advances in the field of carnitine research with respect to mass spectrometric analyses of acyl-carnitines in normal and various pathological states.Conclusion: The growing number of publications using mass spectrometry as a tool to investigate normal physiological conditions or reveal potential biomarkers of primary and secondary carnitine deficiencies shows that this tool brought a new perspective to carnitine research.

Slc22a5 haploinsufficiency does not aggravate the phenotype of the long-chain acyl-CoA dehydrogenase KO mouse.

Secondary carnitine deficiency is commonly observed in inherited metabolic diseases characterised by the accumulation of acylcarnitines such as mitochondrial fatty acid oxidation (FAO) disorders. It is currently unclear if carnitine deficiency and/or acylcarnitine accumulation play a role in the pathophysiology of FAO disorders. The long-chain acyl-CoA dehydrogenase (LCAD) KO mouse is a model for long-chain FAO disorders and is characterised by decreased levels of tissue and plasma free carnitine. Tissue levels of carnitine are controlled by SLC22A5, the plasmalemmal carnitine transporter. Here, we have further decreased carnitine availability in the LCAD KO mouse through a genetic intervention by introducing one defective Slc22a5 allele (jvs). Slc22a5 haploinsufficiency decreased free carnitine levels in liver, kidney, and heart of LCAD KO animals. The resulting decrease in the tissue long-chain acylcarnitines levels had a similar magnitude as the decrease in free carnitine. Levels of cardiac deoxycarnitine, a carnitine biosynthesis intermediate, were elevated due to Slc22a5 haploinsufficiency in LCAD KO mice. A similar increase in heart and muscle deoxycarnitine was observed in an independent experiment using Slc22a5jvs/jvs mice. Cardiac hypertrophy, fasting-induced hypoglycemia and increased liver weight, the major phenotypes of the LCAD KO mouse, were not affected by Slc22a5 haploinsufficiency. This may suggest that secondary carnitine deficiency does not play a major role in the pathophysiology of these phenotypes. Similarly, our data do not support a major role for toxicity of long-chain acylcarnitines in the phenotype of the LCAD KO mouse.

Carnitine Inborn Errors of Metabolism.

Carnitine plays essential roles in intermediary metabolism. In non-vegetarians, most of carnitine sources (~75%) are obtained from diet whereas endogenous synthesis accounts for around 25%. Renal carnitine reabsorption along with dietary intake and endogenous production maintain carnitine homeostasis. The precursors for carnitine biosynthesis are lysine and methionine. The biosynthetic pathway involves four enzymes: 6-N-trimethyllysine dioxygenase (TMLD), 3-hydroxy-6-N-trimethyllysine aldolase (HTMLA), 4-N-trimethylaminobutyraldehyde dehydrogenase (TMABADH), and γ-butyrobetaine dioxygenase (BBD). OCTN2 (organic cation/carnitine transporter novel type 2) transports carnitine into the cells. One of the major functions of carnitine is shuttling long-chain fatty acids across the mitochondrial membrane from the cytosol into the mitochondrial matrix for β-oxidation. This transport is achieved by mitochondrial carnitine–acylcarnitine cycle, which consists of three enzymes: carnitine palmitoyltransferase I (CPT I), carnitine-acylcarnitine translocase (CACT), and carnitine palmitoyltransferase II (CPT II). Carnitine inborn errors of metabolism could result from defects in carnitine biosynthesis, carnitine transport, or mitochondrial carnitine–acylcarnitine cycle. The presentation of these disorders is variable but common findings include hypoketotic hypoglycemia, cardio(myopathy), and liver disease. In this review, the metabolism and homeostasis of carnitine are discussed. Then we present details of different inborn errors of carnitine metabolism, including clinical presentation, diagnosis, and treatment options. At the end, we discuss some of the causes of secondary carnitine deficiency.

Analytical Methods for Quantitative Plasma Carnitine Determination.

Carnitine is an essential molecule for mitochondrial beta-oxidation of long-chain fatty acids and other cellular functions. Several rare, inherited disorders of carnitine metabolism occur in humans, and secondary carnitine deficiency is an important feature in a variety of clinical settings. Many of these conditions can be detected via quantitative analysis of free and esterified carnitine in plasma or urine, which thus offers an effective means for assessing the transport and initial processing of fatty acids. Here, we describe some of the methods most commonly employed for quantification of plasma carnitine and consider some of the advantages and disadvantages of these approaches. © 2019 by John Wiley & Sons, Inc.

Effect of Antiepileptic Drugs on Plasma Carnitine Level in Children with Idiopathic Epilepsy

AbstractBackground: Prolonged antiepileptic drugs treatment can result in secondary carnitine deficiency. Clinical studies indicate a decrease in total and free plasma carnitine level in children treated with old antiepileptic drugs especially val-proate.Aim of Study: Was to evaluate the plasma carnitine level in children with idiopathic epilepsy treated with old antiepi-leptic drugs (valproate and carbamazepine) and new antiepi-leptic drugs (leviteracetam and oxcarbazepine).Patients and Methods: This study was a prospestive study including 50 patients with newly diagnosed idiopathic epilepsy classified into four groups according to their antiepileptic drug treatment into: Group 1, 20 patients received valproic acid. Group 2, 10 patients treated with carbamazepine. Group 3, 10 patients treated with leviteracetam. Group 4, 10 patients treated with oxcarbazepine. The study was carried out in duration of 1 year from January 2017 to January 2018.Results: There was significant difference between mean plasma level of carnitine in children treated with valproate and the controls. There was inverse correlation between the duration of treatment with valproate and the mean plasma carnitine level. There was inverse correlation between the level of valproate and the mean plasma carnitine level. The higher the level of valproic acid, the more significant decrease in the mean plasma carnitine level.Conclusion: Valproic acid was the only antiepileptic drug reported to cause carnitine deficiency. Also this study showed inverse correlation between plasma carnitine level and duration of treatment with valproic acid. The longer the duration of treatment, the more significant decrease in mean plasma carnitine level. Also, there was inverse correlation between the level of valproate and the mean plasma carnitine level. The higher the level of valproic acid, the more significant decrease in the mean plasma carnitine level.

Carnitine Deficiency in Chinese Children with Epilepsy on Valproate Monotherapy

To explore the incidence and independent risk-factors of secondary carnitine deficiency in Chinese children with epilepsy on valproate monotherapy. The free carnitine and acylcarnitines levels in 299 children with epilepsy on valproate monotherapy between June 2014 and September 2015 were compared with age- and sex-matched 299 healthy controls. Children with valproate monotherapy had lower free carnitine levels [23.86 (10.60) µmol/L] than the controls [36.37 (9.37) µmol/L] (P<0.01). Most acylcarnitines were significantly lower in children with valproate monotherapy than controls. 63 children (21.1%) with epilepsy had carnitine deficiency; 54 were asymptomatic. Female gender (OR 2.1), high alanine aminotransferase levels (OR 1.0) and long duration of VPA treatment (1-12 mo) (OR 1.9) were independent risk factors for secondary carnitine deficiency induced by VPA. Carnitine deficiency with valproate is more likely in females, those with transaminitis, and those receiving the drug for 1-12 months.