Hyperhomocysteinemia In Children Research Articles

Association of genetic variants MTHFR A1298C and MTHFR C677T in the methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children with autism spectrum disorder

Association of genetic variants MTHFR A1298C and MTHFR C677T in the methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children with autism spectrum disorder

Polymorphic substitutions in folate cycle genes as predictors of hyperhomocysteinemia in children

Introduction. Mutant alleles of genes of folate cycle enzymes can lead to the significant deterioration of its function and varying severity of pathology. Several defects in these genes lead to severe hyperhomocysteinemia, the most common form of which is a deficiency of cystathionine beta-synthase B. 
 Aim: to establish polymorphic substitutions in the genes of folate cycle enzymes that contribute to the formation of hyperhomocysteinemia in children.
 Materials and methods. Two hundred seventy one children aged of 13–18 years were examined. The analysis of genetic polymorphisms of the folate cycle was carried out using a molecular genetic method. Quantitative determination of the blood homocysteine and folic acid level was performed by chemiluminescent immunoassay on microparticles. Statistical data processing was carried out using Statistica 6.1 application programs (StatSoft Inc., USA). 
 Results. The frequency of the T allele of the MTHFR 677 gene was revealed to be higher in adolescents of the main group compared with the control (p = 0.043). The frequency of the homozygous genotype 66 AA of the MTRR gene in children of the comparison group was significantly higher (p = 0.049), however, the heterozygous genotype 66 AG of the MTRR gene was significantly more often detected in adolescents of the main group (p = 0.008). The average concentrations of homocysteine in children of the main group were 11.6 mmol/L, in adolescents of the control group 9.3 mmol/L (p = 0.021). Hyperhomocysteinemia in children of the main group was detected in 217 (80.1%) adolescents, and in 57 (49.6%) children of the control group (p < 0.001). The baseline serum folate level was determined in the children of the main group. The average amount of vitamin B9 in the blood of children of the main group was 3.7 ng/ml, and in 145 (53.5%) children this indicator was significantly reduced.
 Conclusion. Low levels of folic acid contribute to an increase in homocysteine in blood plasma. Taking vitamin B9 and vitamin folate complexes significantly reduces the level of homocysteine in blood plasma (p < 0.001).

Genetic polymorphisms of the folate cycle and hyperhomocysteinemia in children from areas bordering the Chоrnobyl exclusion zone

The aim of the work is to establish a relationship between polymorphisms of the FC and the state of hyperhomocysteinemia in children living in areas bordering the ChEZ). Research methods: laboratory, genetic, mathematical-statistical. Results: The levels of homocysteine (Hcy) in blood and genetic polymorphisms of the folate cycle (FC) were determined in 690 children (322 boys and 368 girls) aged 8-17 years old living near the ChEZ. It was found that 97.8% of the children had genotypes with risk alleles of FC polymorphisms. The most common combinations of 2 and 3 polymorphic variants. The proportion of hyperhomocysteinemia cases was recorded in 62.5% of those examined and did not generally depend on the number of FC polymorphisms with risk alleles. Unlike their mothers, there was no correlation between blood Hcy concentration and the number of FC polymorphisms with risk alleles in children. The frequency of hyperhomocysteinemia cases in boys was likely higher than in girls. Hyperhomocysteinemia was detected in 40% of cases among children with no risk alleles for FC genetic polymorphisms. Genotypes with allele variants of one FC polymorphism were found in 15% of cases. High frequency of hyperhomocysteinemia was recorded both in the subgroup with T/T MTHFR:677 genotype and in most genetic subgroups. A high frequency of hyperhomocysteinemia, with four polymorphisms with risk alleles, was associated with compound heterozygotes A/CMTHFR:1298 and C/TMTHFR:677 in combination with A/G MTR genotypes: A2756G and G/G A66G. The homozygous variant of the neutral allele A of the MTRR:A66G genetic polymorphism, which controls methionine synthase reductase, contributed to the improvement of Hcy methylation processes in risk allele variants of three FC polymorphisms. Conclusions: The conducted studies indicate that in children of the second Chоrnobyl generation, who have been living in conditions of constant radiation exposure in areas affected by the Chоrnobyl accident since birth, the occurrence of hyperhomocysteinemia is not associated with a specific genotype and the number of FC polymorphisms with risk alleles. The results obtained indicate the participation of genetic and environmental factors in the occurrence of hyperhomocysteinemia in the population of children living in areas located near the ChEZ.

ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ ЭНДОТЕЛИЯ СОСУДОВ ПРИ ГИПЕРГОМОЦИСТЕИНЕМИИ У ДЕТЕЙ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

Background. Homocysteine is a sulfur-containing amino acid that can have a damaging effect on the vascular endothelium, being an independent risk factor for the development of cardiovascular pathology. The purpose. To evaluate the functional state of the vascular endothelium in hyperhomocysteinemia in children with arterial hypertension. Material and methods. 111 children aged 14 to 18 years were examined. All patients were divided into 3 groups:group I (n=51) consisted of children with arterial hypertension, group II (n=30) included those with high normal blood pressure, group III was composed of 30 healthy children. Plasma homocysteine was determined by high-pressure liquid chromatography. Results. Plasma homocysteine concentration increases in patients with high normal blood pressure and arterial hypertension compared with healthy children. Pathological decrease in endothelium-dependent vasodilation is accompanied by an increase in the concentration of homocysteine in the blood plasma.

The role of the deficiency of vitamin B12 and folic acid on homocysteinemia in children with Turner syndrome

Premature atherosclerosis and ischemic heart disease represent a major cause of comorbidities among children with Turner syndrome. The identification of non-traditional risk aspects is crucial for the early identification and management of such comorbidities through establishing effective preventive measures. The aim of the study is to explore the role of the deficiency of vitamin B12, folic acid and homocysteine in children withTurner syndrome. The study included 78 children with Turner syndrome and 67 healthy age and sex matched children. Karyotype was implemented for all patients. The serum levels of vitamin B12, folic acid and serum homocysteine were assessed. The prevalence of the deficiency of vitamin B12 and folic acid was estimated to study its correlation to hyperhomocysteinemia in Turner syndrome children. The karyotype analysis showed 45,X (monosomy X) in the 78 patients. Vitamin B12 and folic acid were significantly decreased in children with Turner syndrome in 65-73% of the patients, respectively, while the serum level of homocysteine significantly increased to 48.7% compared to healthy controls. Homocysteine level negatively correlated with vitamin B12 and folic acid. The deficiency of vitamin B12 and folic acid increased the risk of hyperhomocysteinemia in children with Turner syndrome (OR 2.49 and 2.36, respectively). This report highlights that hyperhomocyste-inemia in children with Turner syndrome may be related to the deficiency vitamin B12 and folic acid.

Hyperhomocysteinemia in children is an indicator of environmental problems associated with the chоrnobyl exclusion zone

The aim of study: determination of the genetic factor’s involvement (MTHFR:C677T polymorphism), which affects the activity of the main enzyme of the folate cycle, methylenetetrahydrofolate reductase, and environmental exposure, including the radiation factor, in the occurrence of hyperhomocysteinemia in children which living near the Chornobyl Exclusion Zone (ChEZ). Research methods. Immunochemical, mathematical and statistical. Results. Within the framework of international projects, the levels of homocysteine (Hcy) and allelic variants of the genetic polymorphism MTHFR:C677T were determined in 624 children aged 13-17 years old from Ivankivskyi and Poliskyi districts of the Kyiv region. It has been established that an increase in the level of Hcy in the blood and an increase in the number of cases of hyperhomocysteinemia in the examined groups of children are associated with forest fires in the ChEZ in 2015 and 2020. Under conditions of pronounced exposure to radioactive agents and combustion products of forest trees, the proportion of cases of hyperhomocysteinemia in groups of children with and without the T allele of the MTHFR:677 polymorphism in the genome did not have statistical differences. An indicator of ecological trouble in the ChEZ and adjacent areas is an increase, above the physiological level, in the concentration of Hcy in the blood of adolescent children with the absence of the T allele of the MTHFR:677 polymorphism in the genome. Conclusion. In areas affected by the accident at the Chornobyl nuclear power plant, it is necessary to constantly conduct regular monitoring studies of the health of children, using tests for the content of Hcy in the blood and the state of the folate cycle genes.

Genetic control of homocysteine metabolism in children living near the chоrnobyl exclusion zone

The aim of study: to determine the involvement of folate cycle genes in the occurrence of hyperhomocysteinemia in children from Ivankivskyi district of Kyiv region of Ukraine 35 years after the accident at the Chornobyl nuclear power plant. Research methods. Immunochemical, mathematical and statistical. Results. Homocysteine levels were determined in 217 children aged 12-17 from Ivankivskyi district of Kyiv region, as well as genetic polymorphisms of the folate cycle. An excess of homocysteine in the blood over 10 µmol/l (a state of hyperhomocysteinemia) was detected in 65.44 % (142 out of 217) of those examined, among boys – 69.79 % (67 out of 96), among girls – 61.98 % (75 out of 121). The largest proportion of hyperhomocysteinemia cases was registered in the subgroup of children with the basic polymorphism MTHFR: 677TT – 94.44 % of cases. In most cases, hyperhomocysteinemia in children was associated with an environmental factor, including radioactive elements and their decay products. The system for the prevention of hyperhomocysteinemia and its consequences in children living in areas affected by the accident at the Chornobyl nuclear power plant should include regular monitoring of the content of radionuclides in the body of children and locally produced food, the content of homocysteine in the blood, and assessment of the state of folate cycle genes.

ДОСЛІДЖЕННЯ ПОКАЗНИКІВ ОКСИДАТИВНОГО СТРЕСУ В НИРКАХ СТАТЕВОНЕЗРІЛИХ ЩУРІВ З ГІПЕРГОМОЦИСТЕЇНЕМІЄЮ

Purpose: Hyperhomocysteinemia in children can develop as a result of genetic defects, endocrine abnormalities or under the influence of dietary factors. An elevated level of homocysteine is considered a risk factor for the progression of chronic kidney disease. The aim of the work was to investigate the indicators of oxidative stress in the homogenate of the kidneys of immature rats in control and with hyperhomocysteinemia. Methods: The concentration of reduced and oxidized glutathione, the activity of superoxide dismutase, catalase and nitric oxide synthase were determined. The model of hyperhomocysteinemia was reproduced on one-month-old male rats, which were kept on a standard vivarium diet. The experimental group was intragastrically administered by D,L-thiolactone homocysteine hydrochloride in a 1% starch solution at a dose of 200 mg/kg of body weight 1 per day for 8 weeks. The corresponding volume of 1% starch solution was injected into the control group of animals. The activity of superoxide dismutase, catalase and nitric oxide synthase were determined spectrophotometrically. Concentration of reduced and oxidized glutathione by fluorometric method. Results: It was established that upon hyperhomocysteinemia the concentration of reduced glutathione, the activity of superoxide dismutase, catalase, and nitric oxide synthase was decreased against the background of an increase in the concentration of oxidized glutathione in the homogenate of the kidneys of immature rats. Conclusions: The obtained results indicate that in the kidneys of immature rats, the development of oxidative stress occurs in the direction characteristic of adult animals. The obtained results indicate that in the kidneys of immature rats the development of oxidative stress resembles the adult animals. The obtained results showed a decrease in the concentration of reduced glutathione and the activity of antioxidant defense enzymes which may indicate the development of pathological processes in the kidneys

Hyperhomocysteinemia in children and forest fires in the Chоrnobyl exclusion zone

Objective: We determined a role of folate metabolism genotypes in the occurrence of hyperhomocysteinemia in children after a forest fire in the Chоrnobyl exclusion zone (ChEZ). Material and methods: In the study, we applied immunochemical, Real-time PCR, mathematical and statistical methods. Results: A survey of 84 adolescents from the Poliske district, Kiev region revealed changes in their metabolic processes in the form of increased homocysteine production in connection with a forest fire in the ChEZ which was recorded during April 26-29, 2015. A comparative analysis of the specific gravity of the folate cycle genotypes in the subgroups of the children with hyperhomocysteinemia before and after a forest fire showed that an endogenous factor in the form of a genetic apparatus, controling synthesis of folate cycle enzymes, was not involved in this phenomenon. Сonclusions: Forest and peat fires in the Chernobyl exclusion zone are one of the main causes for the elevation in blood homocysteine levels in children from the adjacent districts, regardless of the state of folate metabolism genetic system. Monitoring of the blood homocysteine levels in children and adults living under conditions of the exposure to wood combustion gases, containing radioactive elements, is a key component of the programmer for the prevention of cancer and cardiovascular diseases.

Hyperhomocysteinemia in children with pyelonephritis

Objective: to examine the blood levels of homocysteine in children with different courses of chronic pyelonephritis. The study covered 60 children with secondary chronic pyelonephritis. Homocysteine levels were estimated using an Immulite-2000 system (Siemens Healthcare Diagnostics Inc., USA). Statistical nephroscintigraphy was used to detect the foci of nephrosclerosis. The mean homocysteine level in the children with pyelonephritis was 7,9±4,27 μmol/L; at the same time this did not statistically differ from that observed in healthy children (6,1±2,8 μmol/L) have been identified. Significant differences were obtained only between children with signs of sclerosed kidney tissue and those without the signs (9,68±5,23 and 5,97±0,9; р=0,001); this was typical of all age groups. Detection of hyperhomocysteinemia in children with chronic pyelonephritis determines their allocation to a group at risk for early nephrosclerosis.

P282 – 1760 The hyperhomocysteinemia in children treated by antiepileptic drugs

P282 – 1760 The hyperhomocysteinemia in children treated by antiepileptic drugs

PW01-191 - Hyperhomocysteinemia in children and adolescents with psychotic and mood disorders

The aim of our study was to get information about serum level of homocysteine (Hcy) for patients with schizophrenia spectrum, patients with affective disorders and in control group.MethodsFor the studies, we have used 225 patients from Children's Psychiatric Hospital. 82 of all selection were with schizophrenia spectrum disorders, 27 patients with affective disorders and 116 patients came from control group.Patients were selected according to their diagnosis (in line with ICD-10) and current clinical status. Each diagnosis and clinical status was coded depending on its severity and course of disease.The level of Hcy was stated by isocratic HPLC system with fluorometric detection (Shimadzu LC-20, model RF-10AxL).ResultsCorrelation of Hcy concentration between schizophrenia's spectrum disorders and control group was r = -0.39 (p< 0.001; t = 22.99).Mean level of Hcy was 11.94 μmol/L for patients with schizophrenia's spectrum disorders and 11.55 μmol/L for patients with affective disorders versus 7.47 μmol/L in control.It has been found that the highest level of Hcy in the group of schizophrenia spectrum disorders has been seen in patients with episodic-recurrent course of disease, especially with pronounced affect. For the group with affective disorders the highest level was seen in patients with depressive symptoms with anxiety and mixed affective disorders (r = 0.58; p< 0.001; t = 12.77).ConclusionsObtained data are indicative of potential link among the level of Hcy and schizophrenia, and that the level of Hcy is inwrought with affective disorders and anxiety in the course of disease.

Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.

Plasma Total Homocysteine Levels in Children with Type 1 Diabetes: Relationship with Vitamin Status, Methylene Tetrahydrofolate Reductase Genotype, Disease Parameters and Coronary Risk Factors

The objectives of this study were: to determine plasma total homocysteine tHcy levels and the prevalence of hyperhomocysteinemia in children with type 1 diabetes, to determine correlates of plasma tHcy levels with nutritional factor such as serum folic acid and vitamin B12 levels, genetic factors as methylenetetrahydrofolate reductase MTHFR gene polymorphism (C677T and A1298C), to attempt to identify possible dependencies between tHcy and the degree of metabolic control, the duration of the disease and presence of complications, and also to determine the relationship between other coronary risk factors. Plasma tHcy levels and other related parameters performed in 32 children with type 1 diabetes and 23 age-sex matched healthy children. Median tHcy level was higher in the patient group (11.38, 3.28 to 66.01 micromol/l) than the control group (8.78, 1.06 to 13.66 mol/l) (p < 0.05). A 28.1 per cent (n = 9) of the diabetic patients had hyperhomocysteinemia, four case with mild and five case with moderate. Plasma tHcy levels were positively correlated with disease duration and C-reactive protein CRP levels and negatively correlated with disease onset age. The hyperhomocysteinemic group had higher CRP levels, longer disease duration and early onset of disease than non-hyperhomocysteinemic group (p < 0.05 in both), respectively. The hyperhomocysteinemic group had significantly higher CRP, total cholesterol, triglyceride, apolipoprotein B, systolic blood pressure, blood urea nitrogen and creatinine levels and lower folate, apolipoprotein A1 levels and glomerular filtration rate values than the control group. Plasma tHcy levels were higher in diabetic children with poor metabolic control. Because of hyperhomocysteinemia is common in diabetic children and plasma tHcy levels correlated with early onset of the disease and disease duration, we recommend the usage of plasma tHcy levels as a risk indicator parameter with other coronary risk factor for detecting and preventing cardiovascular disease in diabetic children.

Homocysteine binds copper and induces COX deficiency and apoptosis in different neuron-like cell culture models preventable by copper supplementation

Objective: Severe hyperhomocysteinemia in children with hereditary homocystinuria often presents with a variety of neurological symptoms like mental retardation and seizures, and mild hyperhomocysteinemia has been associated with neurological impairment of the elderly. The causative link of hyperhomocysteinemia and neurological dysfunction is unknown.

Hyperhomocysteinemia in Children Treated with Antiepileptic Drugs Is Normalized by Folic Acid Supplementation

To assess the prevalence of hyperhomocysteinemia in pediatric patients treated with antiepileptic drugs (AEDs) and to evaluate the effect of folic acid supplementation on plasma total homocysteine (tHcy) concentrations in hyperhomocysteinemic patients. 123 patients from three regional hospitals participated in the study. Patients with hyperhomocysteinemia were included in a 3-month double-blind randomized trial testing oral folic acid supplementation (1 mg/day) versus placebo. Hyperhomocysteinemia (tHcy >10.4 micromol/L) was present in 19 of 123 patients. Patients with hyperhomocysteinemia were older (13.7 +/- 4 vs. 11.0 +/- 3.9 years) and had significantly lower folate and cobalamin concentrations. Multidrug (two or more) AED treatment and duration of therapy correlated significantly with elevated total homocysteine (tHcy) and low folate. In contrast, polymorphisms in the methylene tetrahydrofolate reductase gene (MTHFR 677 C-->T, 1298 A-->C, 1793 G-->A) had no significant impact on tHcy. Nine of 19 patients with hyperhomocysteinemia were randomized to placebo, whereas the remaining 10 patients received folic acid supplementation. Folic acid supplementation resulted in a significant increase of folate and decrease of tHcy, whereas both parameters remained unchanged in the placebo group. Hyperhomocysteinemia is present in 15.5% of children receiving long-term AED treatment. Multidrug treatment and long duration of therapy enhance the risk for hyperhomocysteinemia. Folic acid supplementation significantly reduces tHcy. We recommend assessment of serum folate and plasma tHcy in children receiving AEDs.

Hyperhomocysteinemia in children on renal replacement therapy.

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hcy) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hcy levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hcy, red blood cell (RBC) folate, and serum vitamin B(12) levels were measured. The plasma Hcy levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hcy level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation ( r=-0.49) between plasma Hcy levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 micro g/ml) and normalization of the plasma Hcy levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hcy level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hcy level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hcy concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hcy concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hcy levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hcy levels and should be added to the medical treatment of all children with impaired renal function.

Hyperhomocysteinemia in children with renal transplants.

Many studies have demonstrated a strong association between elevated plasma total homocysteine (tHcys) levels and vascular disease. The aim of the present study was to determine the plasma levels of tHcys in pediatric recipients of renal transplants, to establish possible correlations with renal function, lipid profile, and folate and vitamin B12 status, and to assess whether the C677T and A1298C polymorphisms in the 5, l0-methylenetetrahydrofolate reductase (MTHFR) gene were associated with a particular risk. A total of 26 transplanted children and adolescents were investigated. tHcys levels were elevated in transplanted patients (12.9+/-4.8 micro mol/l) and 73% of these displayed values above the 97th percentile of healthy children. Plasma tHcys correlated negatively with creatinine clearance ( r=-0.58, P<0.001) and plasma vitamin B(12) ( r=-0.40, P<0.05) and positively with plasma triglycerides ( r=0.53, P<0.005). No significant correlations were found between plasma tHcys level and age, gender, time elapsed after transplantation and plasma values of glucose, insulin, folic acid, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, apolipoprotein B, and apolipoprotein A-1. Plasma tHcys level was clearly increased in 3 patients with a MTHFR 677TT/1298AA genotype. In a multiple stepwise regression model plasma creatinine and triglyceride levels and MTHFR 677TT/1298 AA genotype accounted for 60% of the observed plasma tHcys variability. The MTHFR 677CT/1298 AC genotype was not a significant predictor of tHcys plasma levels. We conclude that a moderate degree of hyperhomocysteinemia is often present in renal transplant children and that folate supplementation must be considered in this population.

Hyperhomocysteinemia in children treated with sodium valproate and carbamazepine

Objective: To evaluate plasma homocysteine (Hcy) concentrations in children receiving sodium valproate (VPA) and carbamazepine (CBZ), monotherapy, in comparison with healthy control subjects and to determine the possible relationship between Hcy levels and dosage and plasma concentrations of the antiepileptic drugs. Methods: We measured levels of fasting and post-methionine Hcy, plasma pyridoxal 5′-phosphate (PLP, active vitamin B6), serum folate, erythrocyte folate and serum vitamin B12 in 60 epileptic patients (29 females, 31 males), aged from 14.2 to 17.9 years, subdivided into two groups according to their therapy. Sixty-three healthy sex- and age-matched children served as controls. These measurements have been performed before the beginning of therapy and after 1 year of therapy with VPA or CBZ. Results: Before the beginning of therapy, there were no significant differences in fasting and post-methionine Hcy, plasma PLP, serum folate, erythrocyte folate and serum vitamin B12 values between the control group and the two groups of epileptic children. After 1 year of therapy, patients treated with VPA and CBZ showed a significant increase of the plasma concentrations of Hcy when compared to baseline data and controls values. Moreover, was observed a significant decrease of serum folate and plasma PLP. On the contrary, serum vitamin B12 and erythrocyte folate levels remained in the normal range. Conclusions: Our study demonstrates that prolonged treatment with VPA and CBZ increases plasma concentrations of Hcy.

Selective Screening for Hyperhomocysteinemia in Pediatric Patients

Hyperhomocysteinemia is a common condition with genetic and environmental causes (1), and associated, especially in its severe form, with risk of premature atherosclerosis and thrombosis (2). Testing for hyperhomocysteinemia in children may be useful for investigation of patients with clinical features of homocystinuria (2), and for the assessment of nutritional status (3). Moreover, the investigation of causes of mild hyperhomocysteinemia, such as diabetes (1) or renal failure (4), may clarify the etiology of this abnormality. The possibility of easily correcting hyperhomocysteinemia by diet suggests potential utility of screening within some populations (5). Screening for hyperhomocysteinemia in children has rarely been reported. In infants, total homocysteine (tHcy) measurement was reported only in a group on macrobiotic diets (6) and, in children, in a group with leukemia (7). Recently, a group of children with premature cardiovascular death in their male relatives was studied and the modest increase of plasma tHcy was partly attributed to genetic factors (8). Our aim was to screen for hyperhomocysteinemia in children at risk, owing to genetic or environmental causes, (a) to discover individual patients with primary hyperhomocysteinemia and (b) to compare tHcy concentrations of certain groups of children at risk with those of age-matched reference values. Screening was performed in the following …