Serum Carnitine Levels Research Articles

The First Case of 3-Methylcrotonyl-CoA Carboxylase (MCC) Deficiency Responsive to Biotin

3-Methylcrotonylglycinuria is an inborn error of leucine catabolism with an autosomal recessive pattern of inheritance that results from a deficiency of 3-methylcrotonyl-CoA carboxylase (MCC). We report on a nine-year-old boy with severe psychomotor retardation who developed infantile spasms at the age of three weeks. Urine analysis at the age of two years revealed massive 3-methylcrotonylglycinuria and 3-hydroxyisovaleric aciduria suggesting MCC deficiency. Carnitine serum levels were decreased. Biotin therapy led to a dramatic decrease in the frequency of seizures, disappearance of hypsarrhythmia, and near normalisation of organic aciduria. Four months later a protein-restricted diet was introduced in addition and the boy remained clinically and metabolically stable. However, severe psychomotor delay persisted, and the seizures partially reoccurred. Biochemical findings showed partial MCC deficiency in cultured fibroblasts. Molecular genetic studies revealed a heterozygote missense mutation, MCCA-R385S, converting arginine to serine in a highly conserved region of the MCCA gene. This is the first patient with MCC deficiency caused by a heterozygote mutation and who demonstrated a substantial and sustained clinical and biochemical response to therapeutic doses of biotin. Sadly, this patient again also demonstrates that the main determinant of the outcome of even easily treatable metabolic diseases is timely diagnosis.

SERUM CARNITINE LEVELS IN CHILDREN WITH IRON-DEFICIENCY ANEMIA WITH OR WITHOUT PICA

Carnitine is ingested through animal-derived foods as well as synthesized in vivo. It plays an important role in the energy metabolism of many tissues. Iron acts as a co-factor for the synthesis of carnitine. However, the importance of iron deficiency as a cause of secondary carnitine deficiency is not well established. The aim of this study was to investigate the serum levels of carnitine in children with iron-deficiency anemia compared to those of healthy children and to determine if serum carnitine levels in with or without pica differ. The mean serum carnitine concentration in the iron-deficiency group was significantly lower than that in healthy children (12.44± 5.09 and 32.48 ± 7.92 μmol/L, respectively, p <. 001). In the iron-deficient group, serum carnitine levels, ferritin levels, and other hematological parameters were lowest in patients with pica (p <. 001). Pearson correlation test indicated a positive correlation between serum carnitine and ferritin levels in iron-deficient patients. Based on the evidence about the effect of low iron on carnitine stores in animal studies, the authors propose that low serum carnitine levels in these children may be secondary to iron-deficiency anemia. However, further large-scale studies are needed to establish the frequency of carnitine deficiency in children with iron-deficiency anemia.

ANTIEPILEPTIC DRUG THERAPY AND SERUM CARNITINE LEVELS IN CHILDREN PRIOR TO AND FOLLOWING TREATMENT

Background: The physiologic function of carnitine, oxidation of fatty acid and lipid metabolism, is severely affected in carnitine deficiency, secondary forms of which lead to renal tubular disorders and chronic renal failure. Reduction in serum carnitine has been frequently reported in patients and experimental animals treated with antiepileptic drugs, one of which, valproic acid has consistently been found to cause the deficiency; the antiepileptic drugs, valproic acid, has consistently been found to cause the deficiency. Previous results, however, regarding the effects of other antiepileptic drugs have been less consistent. Considering the controversial results available in lterarure, the aim of this study was to determine the effect of Valproic acid, Carbamazepine and Phenobarbital on serum carnitine levels in epileptic children. Methods: In the present study, serum carnitine levels were randomly monitored before and six months after therapy in 39 epileptic patients receiving the antiepileptic drugs mentioned. Patient blood samples were taken before and six months after treatment and L-carnitine level was determined using the UV enzymatic test (Rouche Kit) spectronic Genesis 2, 340 nm. Results: Results showed a significant fall in the L-carnitine levels of epileptic children taking these drugs (P Conclusion: Considering the reducing effect of antiepileptic drugs on serum carnitine levels, it is recommended that a carnitine supplement be administered in pediatric epileptic patients to prevent the deficiency and related consequences caused by such therapies. Keywords: Carnitine ,Epilepsy - in children ,Valproic Acid, Phenobarbital, Carbamazepine

Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. Fifty-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. When the cachectic patients with gastro-intestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 micromol/L in free carnitine (P < 0.005), 0.04 micromol/L in long chain acylcarnitine (P < 0.05), 8.7 micromol/L in total carnitine (P < 0.001). In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 micromol/L in free carnitine (P < 0.001), 4.60 micromol/L in short chain acylcarnitine (P < 0.001), and 0.60 micromol /L in long-chain acylcarnitine (P < 0.005) and 17.4 micromol/L in total carnitine (P < 0.001). In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 micromol/L in free carnitine (P < 0.001), 5.2 micromol /L in short-chain acylcarnitine (P < 0.001), 1.0 micromol/L in long chain acylcarnitine (P < 0.001), and 21.8 micromol/L in total carnitine (P < 0.001). Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

Serum carnitine levels in patients with tumoral cachexia

Background Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. Methods Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. Results In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was − 8.20 μmol/L ( p = 0.000); the difference in short-chain acylcarnitine − 2.60 μmol/L ( p = 0.029); the difference in soluble acid carnitine − 10.80 μmol/L ( p = 0.000); the difference in long-chain acylcarnitine − 0.40 μmol/L ( p = 0.036); and the difference in total carnitine −11.20 μmol/L ( p = 0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was −5.80 μmol/L ( p = 0.006); the difference in soluble acid carnitine − 7.20 μmol/L ( p = 0.000); and the difference in total carnitine − 7.50 μmol/L ( p = 0.000). Conclusion Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients.

Carnitine deficiency in patients with coeliac disease and idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDCM) and coeliac disease (CD) are two pathological conditions which may lead, by different mechanisms, to malabsorption of various micronutrients, including carnitine, active in cardiac metabolism. The aim of the present investigation was primarily to evaluate differences in serum concentrations of total carnitine between IDCM patients and patients with IDCM associated with CD and then also to evaluate, in the latter, the effect of a gluten-free diet on serum concentrations of total carnitine. Serum carnitine was determined by enzymatic spectrophotometric assay in three groups of individuals: group A, 10 patients (5 males, 5 females), mean age 46.5+/-10.8 years, presenting isolated IDCM; group B, 3 patients (2 males, 1 female), mean age 34+/-8 years, with IDCM+CD; and group C, 10 healthy subjects (5 males, 5 females), mean age 38.6+/-11.1 years. All patients with IDCM belonged to class NYHA I-II. Mean concentrations of total serum carnitine in the group of patients with isolated IDCM (group A) were found to be lower than in the controls (group C). The concentrations in patients with IDCM associated with CD (group B) were lower than in the control group and also lower than in the isolated IDCM (group A). After 2 years on a gluten-free diet, patients presenting IDCM associated with CD showed a progressive increase in mean serum carnitine levels compared to values observed prior to the diet. Patients presenting IDCM associated with CD show a greater decrease in serum total carnitine levels than patients presenting the isolated form of IDCM. A gluten-free diet, in these patients, leads to a progressive increase in serum levels of this substance.

The effect of oral L‐carnitine supplementation on the lipid profiles of hyperlipidaemic children

To investigate the carnitine status and the effect of carnitine supplementation on serum lipid profiles in children with hyperlipoproteinaemia, a clinical open trial was conducted at Hacettepe University Ihsan Dogramaci Children's Hospital, Section of Nutrition and Metabolism. Patients were given carnitine at a dose of 100 mg/kg/d for 12 wk. Blood samples for the determination of lipid profile and carnitine levels and urine samples for carnitine levels were obtained on admission, at week 4 and week 12 of the study period. A total of 41 children were enrolled in the study: 20 patients had type II heterozygotes, eight patients had type II homozygotes, three patients had type III, six patients had type V and four patients had secondary hyperlipidaemias. Serum and urine carnitine levels were within normal limits on admission. No significant correlations were found between serum carnitine levels and serum lipid profiles. Serum HDL and apolipoprotein A-I decreased significantly during the 12 wk of intervention in type II heterozygotes. In type II homozygotes, total cholesterol and LDL levels at weeks 4 and 12 increased significantly compared to initial levels. No significant change was noted for lipid parameters in hyperlipoproteinaemia type V. The results of this trial demonstrated that carnitine supplementation was of no benefit for children with hyperlipidaemias, especially in primary hyperlipoproteinaemia type II heterozygotes, homozygotes and type V.

Relative Carnitine Deficiency in Autism

A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine (p < 0.001), and pyruvate (p = 0.006) were significantly reduced while ammonia and alanine levels were considerably elevated (p < 0.001) in our autistic subjects. The relative carnitine deficiency in these patients, accompanied by slight elevations in lactate and significant elevations in alanine and ammonia levels, is suggestive of mild mitochondrial dysfunction. It is hypothesized that a mitochondrial defect may be the origin of the carnitine deficiency in these autistic children.

Serum carnitine levels in patients with homozygous beta thalassemia: a possible new role for carnitine?

Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) facilitates the transfer of activated long-chain fatty acids from the cytoplasm to the mitochondria, the site of their beta-oxidation. Carnitine deficiency results in a reduced usage of fatty acids in energy production and therefore the appearance of clinical symptoms such as myalgia and muscle weakness. In the present study, serum carnitine levels were measured in 45 children and 20 adults with homozygous beta thalassemia. A decrease in serum carnitine levels (total, free and acyl) was found, without any evidence of disorder in the process of mitochondrial beta-oxidation. The possible cause of this finding could be related to a reduced hepatic carnitine biosynthesis. In patients with homozygous beta thalassemia, the reduction of serum carnitine levels might play an important role in the appearance of muscular dysfunction. It is possible that L : -carnitine administration in these patients might improve or even resolve the aforementioned symptom.

Primary carnitine deficiency: adult onset lipid storage myopathy with a mild clinical course

We studied two adult patients with myalgia and muscular fatigability during prolonged physical exercise. Serum creatine kinase was increased and muscle biopsy revealed a lipid storage myopathy affecting predominantly the type I fibres. Skeletal muscle carnitine content was reduced to 15% and 21% of the normal mean values, while serum carnitine levels were either normal or decreased. Four months of oral therapy with L-carnitine (3 g per day) resolved the clinical symptoms completely in both patients, and a subsequent muscle biopsy confirmed a marked reduction of lipid storage, along with increased muscle carnitine levels. The analysis of renal carnitine excretion and the exclusion of possible secondary carnitine deficiencies in both patients are compatible with mild defects of the carnitine transporter in one patient and of carnitine biosynthesis in the other. Since myalgia and muscular fatigue are frequent but unspecified complaints of otherwise clinically unremarkable adult patients, it is important to identify myopathies associated with primary carnitine deficiency because they may be amenable to treatment.

Serum Carnitine Levels in Newborns with Perinatal Asphyxia and Relation to Neurologic Prognosis

Neonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group ( p =0.014 and p =0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age.

Miopatía por déficit de carnitina: un caso de diagnóstico tardío

Myopathies caused by lipidic metabolism alterations are very infrequent. Carnitine deficiency-associated myopathies are included in this group. Two main types of carnitine deficiency syndromes have been delineated: a predominantly myopathic form, with normal serum and low muscle carnitine levels, and a systemic form, with encephalopathy, hepatic dysfunction, muscle weakness and low muscle, liver and serum carnitine levels. Both types have typical lipid stores in muscle biopsy. We describe the case of a myopathic form of carnitine deficiency. Due to the age of the patient, this is an unusual case, with an unfavourable evolution. Therapeutic measures used in these patients have included prednisone, carnitine replacement and a low-fat with medium chain tryglycerides and high-carbohydrate diet. However, in none of the patients responding to therapy, a significative increase in muscle carnitine has been demonstrated.

Protective effects of carnitine in an experimental ischemia–reperfusion injury

Background/Aims: We aimed to determine the role of exogenous carnitine to prevent ischemia–reperfusion damage in liver tissue in experimental model. Methods: Rats were divided into four groups as Sham (SG), 30% Hepatectomy (HG), ischemia–reperfusion +30% hepatectomy (IRHG) and ischemia–reperfusion+30% hepatectomy+carnitine (IRHCG). Serum AST, ALT and GGT levels have been determined in systemic blood samples (post-hepatic vena cava) and liver tissue and serum carnitine levels in blood samples from portal vein (pre-hepatic blood samples). Results: Serum carnitine levels were significantly higher in IRHCG compared to SG (P < 0.01). Each of the serum AST, ALT and GGT levels were statistically higher in HG, IRHG and IRHCG than SG (P < 0.001). While these values in IRHG were also higher than those in HG (P < 0.001), in IRHCG enzyme levels were significantly lower than IRHG (P < 0.001). Liver tissue damage was less in IRHCG than IRHG statistically (P < 0.001). Conclusions: This animal model implies that exogenous carnitine supplementation may be helpful in preventing free oxygen radical damage and inflammatory reactions in liver tissue.

THE INFLUENCE OF l-CARNITINE SUPPLEMENTATION ON HEMATOCRIT AND HEMOGLOBIN LEVELS IN PATIENTS WITH END STAGE RENAL FAILURE ON CAPD

The influence of l-carnitine supplementation on hematocrit (Hct) and hemoglobin (Hb) levels, in patients suffering from end stage renal disease (ESRD) on maintenance hemodialysis, are well known from several studies. The data concerning the serum levels of carnitine, in patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support that they are rather normal. In this study the effect of l-carnitine supplementation on Hct, and Hb levels were investigated in patients suffering from ESRD on CAPD. In the study 12 patients were included (5 F, 7 M), aged from 39 to 92 years old (median 65.5 years), who were on CAPD for more than 6 months (from 6 to 15 months, mean ± SD = 8.6 ± 3.6), with normal serum ferrum and ferritin levels at the beginning of the study. Two grams of l-carnitine/day per os (Superamin, Vianex Hellas), were administered in all the patients and the serum ferrum levels were tried to be kept stable, by exogenous ferrum administration, during the study period. If the Hct levels were more than 36% per month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and after the first, second and third month of the study period. Finally, the rHuEpo dose/patient was registered monthly before and during the study. During the observations, Hct (35.4 ± 3.3 vs. 38.1 ± 3.4, ANOVA, p < 0.03) and Hb levels (11.0 ± 1.1 vs. 11.9 ± 1, ANOVA, p < 0.01), were significantly increased. On the other hand, rHuEpo dose necessity/patient/week was decreased significantly (3833 ± 3326 vs. 1292 ± 1712, ANOVA, p < 0.01), in order to succeed the target Hct level. Furthermore, red blood cells IR also appeared to have a significant decrease (16.6 ± 7.4 vs. 13.0 ± 3.9, paired t-test, p < 0.03). Finally, the ferrum and ferritin levels were stable during the study period. It was concluded, that in patients on, CAPD the per os l-carnitine supplementation decreased, the red blood cells IR which contributes to the: (a) Increase of Hct and Hb levels and (b) decrease of the patients rHuEpo dose/week.

Clinical and demographic predictors of exercise capacity in end-stage renal disease.

Patients on maintenance hemodialysis therapy for end-stage renal disease have reduced exercise tolerance. Multiple processes related to uremia and hemodialysis have been implicated in the pathophysiology of this impairment. However, limited data are available to identify the separate and combined effects of clinical factors on the degree of impairment for individuals within this population. For this purpose, data from 193 patients who had undergone exercise testing for two clinical trials were retrospectively analyzed. Univariate and multiple linear regression analyses were used to identify demographic and clinical correlates of peak exercise oxygen uptake (VO2). Peak VO2 averaged 18.5 +/- 6.4 mL/min/kg. On univariate analysis, peak VO2 correlated positively with male sex and hemoglobin, serum albumin, and serum creatinine concentrations and correlated negatively with dialytic age and diagnosis of diabetes or chronic heart failure. In a multiple linear regression model, sex, hemoglobin concentration, age, and diagnosis of diabetes each remained statistically significant. Together, factors included in the model accounted for 41% of the variability in peak VO2 (P = 0.0001). Among factors not correlating significantly with peak VO2 were resting blood pressure, serum carnitine level, and urea clearance assessed by Kt/V. Findings show the range of exercise impairment among clinically stable ambulatory hemodialysis patients, which may be sufficient to interfere with normal daily activities for many of these patients. Although this impairment may be broadly attributable to physiological consequences of uremia, the degree of impairment for individual patients is predicted by demographic factors, coexistent disease, and factors potentially modified by medical therapeutics.

SERUM CARNITINE LEVELS OF PEDIATRIC CANCER PATIENTS

Secondary carnitine deficiency may occur in some diseases including malnutrition. The present study examined the serum carnitine levels of children with cancer and their relationship with nutritional status. Fifty-one (mean age: 104 - 23 months) patients with cancer were evaluated at diagnosis and 3 months after the initiation of the treatment. There were significant differences between the mean carnitine levels of patients before and during the treatment ( p : .004). Although initial carnitine levels of patients were similar to those in control groups, there was a significant difference between the mean carnitine levels of patients and those of the control group at the third month ( p : .02). The prevalence of malnutrition at the third month of the treatment (43%) was higher from the prevalence at diagnosis (33%) but this was not significant. No significant relationship was found between carnitine levels and nutritional status of patients either at diagnosis or during treatment. These results showed that inadequate intake of carnitine or its precursors could not be responsible for decrease in carnitine levels. Metabolic changes that result from therapy and/or from neoplastic process may be responsible for the decrease in carnitine levels. Detailed studies, including measurements of fractions of carnitine and urinary carnitine excretion according to individual drug, are necessary to determine real cause of this decrease.

LOW SERUM CARNITINE CONCENTRATIONS IN HEALTHY CHILDREN WITH IRON DEFICIENCY ANEMIA

Carnitine is not only obtained from animal-derived foods but also synthesized in the body. It plays an important role in the energy metabolism of many tissues, including heart and skeletal muscles. Iron is known to be essential for the biosynthesis of carnitine. Although many conditions are well known to cause secondary carnitine deficiency, iron deficiency, which is a very common condition in children, is not well studied as a cause of secondary carnitine deficiency in humans. This study demonstrates the coexistence of iron deficiency and low carnitine levels in otherwise healthy children. The mean carnitine concentration of 18 otherwise healthy children with iron deficiency anemia was significantly lower compared to the mean carnitine concentration of healthy children without iron deficiency anemia. Based on the evidence about the effect of low iron on carnitine stores in experimental animals, we proposed that low serum carnitine levels in these children may be secondary to iron deficiency. However, further studies need to be done to further clarify this relationship.

Carnitine levels in colon, muscle and serum of rats with experimental colitis

Carnitine levels in colon, muscle and serum of rats with experimental colitis

Can serum carnitine levels distinguish hypertrophic cardiomyopathy from hypertensive hearts?

Although echocardiography is a useful diagnostic tool in hypertrophic cardiomyopathy (HCM), it is sometimes difficult to differentiate it from hypertensive heart disease (HHD): some patients with HCM show symmetrical hypertrophy, whereas patients with HHD sometimes show asymmetrical septal hypertrophy. We used a radioiodinated long-chain fatty acid tracer to visualize the altered myocardial fatty acid metabolism of HCM and HHD. Carnitine is the essential substance for the beta-oxidation of long-chain fatty acids. We recently reported that serum free carnitine levels in HCM were elevated and that they were significantly correlated with the severity of myocardial fatty acid metabolic disorder. Therefore, we investigated serum carnitine levels in patients with HCM and HHD, which can contribute to the differentiation of each other. We studied 56 patients with HCM and 20 patients with essential hypertension. Serum free carnitine levels were significantly higher in patients with HCM than those with HHD (HCM 52.5+/-9.5 nmol/mL, HHD 46.6+/-6.4 nmol/mL, P<0.01), but they showed no statistical difference between patients with HHD and normal subjects. Serum acylcarnitine levels were significantly lower in patients with HCM than those with HHD (HCM 10.1+/-4.0 nmol/mL, HHD 14.5+/-4.9 nmol/mL, P<0.0005), although they did not differ between patients with HHD and normal subjects. Scintigraphic analyses with a long-chain fatty acid analog revealed that myocardial tracer uptake was much reduced in patients with HCM compared with that in patients with HHD (quantitative analysis: HCM 2.11+/-0.12, HHD 2.22+/-0.17, P<0.05; semiquantitative analysis: HCM 13.6+/-6.3, HHD 2.0+/-1.5, P<0.0001). In conclusion, the differences in serum carnitine levels between HCM and HHD reflect altered myocardial fatty acid metabolic impairment, and the levels can help to distinguish these 2 diseases.

Carnitine levels in colon, muscle and serum of rats with experimental colitis

Carnitine levels in colon, muscle and serum of rats with experimental colitis