Homocysteine In Children Research Articles

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).

Consumption of very low-mineral water may threaten cardiovascular health by increasing homocysteine in children.

Homocysteine (Hcy) is a critical factor for cardiovascular injury, and the elevation of Hcy in children will inevitably increase the risk of cardiovascular disease in adulthood. This study explored the effect of very low-mineral water on children's Hcy and cardiovascular health. This was a retrospective cohort study that recruited two groups of 10-13-year-old children who had consumed direct drinking water (DDW) in school for 4 years. The control group (NW) (119 boys, 110 girls) consumed normal DDW (conductivity 345 μs/cm). The very low-mineral water consumption group (VLW) (223 boys, 208 girls) consumed very low-mineral DDW (conductivity 40.0 μs/cm). Serum Hcy, Hcy metabolites, cofactors of Hcy metabolism, and cardiovascular biomarkers were assessed and standardized by age- and sex-specific Z-scores, and the differences between the two groups were analyzed with independent t-test. The relationships between Hcy metabolism biomarkers and key factors, cardiovascular biomarkers, serum Ca, and mineral intake were analyzed with linear regression. Compared with the NW group, the VLW group had significantly higher serum Hcy, Apo-B, Apo-B/A1, and oxLDL, and lower serum 1,25,(OH)2D3, vitamin B6 and B12, 5-methyltetrahydrofolate, and Apo-A1. Serum Hcy was positively associated with serum Apo-B and Apo-B/A1, and negatively associated with Ca intake from water and serum 1,25,(OH)2D3. This study suggested that drinking very low-mineral water may increase Hcy level and oxidative stress, worsen lipid profile, and threaten the cardiovascular system in children. Reducing 1,25,(OH)2D3, and disordering of calcium metabolism might play important roles. This study first established an association between demineralized drinking water and cardiovascular health in children, suggesting a new environmental concern risk to cardiovascular health.

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.

Relationship between sleep problems and chronotypes of children and adolescents with attention deficit and hyperactivity disorder and serum GABA, glutamate and homocysteine levels

ABSTRACT In this study, we aimed to determine the relationship between chronotype, sleep problems and serum levels of GABA (gamma amminobutyric acid), glutamate and homocysteine in children and adolescents diagnosed with attention deficit and hyperactivity disorder (ADHD) as well as factors affecting this relationship. Sleep problems of 46 children and adolescents aged 7–18 years diagnosed with ADHD and 30 healthy volunteers aged 7–18 years were evaluated with Children’s Sleep Habits Questionnaire (CSHQ) while chronotypes were evaluated with Children’s Chronotype Questionnaire (CCQ). Serum glutamate, GABA and homocysteine levels were measured using immunosorbent test (ELISA) kits. Sleep problems were significantly more common in the ADHD group compared to the control group (p < .001). Serum GABA, glutamate and homocysteine levels were found to be predictor biomarkers for ADHD, independent of total sleep problem score. When the homocysteine levels were above the cut-off point of 9.445 µmol/L, the sensitivity in early diagnosis of ADHD was 84.8% and the specificity was 70.0%. Although ADHD is a disorder in which sleep problems are common, increased serum GABA, glutamate and homocysteine are important in diagnosing ADHD independent of ADHD-related sleep problems. Homocysteine levels may be an important predictor for the presence of ADHD.

&lt;p&gt;Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls&lt;/p&gt;

ObjectiveWe aimed to investigate the serum concentrations of vitamin B12, folate and homocysteine in children diagnosed with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and healthy controls.Materials and methodsSerum vitamin B12, folate and homocysteine concentrations were measured in 118 children (48 children diagnosed with ADHD, 35 children diagnosed with ASD and 35 healthy controls). Symptom severity in the ADHD and ASD groups was evaluated by the Childhood Autism Rating Scale and Turgay-DSM-IV-Based Screening and Assessment Scale for Disruptive Behavior Disorders. Multivariate analysis of covariance was used to evaluate the effects of diagnosis and gender on biochemical parameters.ResultsThe ADHD and ASD groups and the healthy controls differed significantly regarding vitamin B12 and homocysteine concentrations, but not folate levels. Patients with ASD had the lowest vitamin B12 and the highest homocysteine levels. Vitamin B12 levels correlated negatively with hyperactivity and/orimpulsivity and oppositionality symptoms in children with ADHD. There were no relationships between psychometric evaluations and laboratory measurements in children with ASD. Gender did not affect vitamin concentrations.ConclusionPrevious studies found that vitamin B12 was reduced while homocysteine was elevated among patients with ADHD and ASDs. Our results also support those reported previously. Oppositionality and hyperactivity and/orimpulsivity may be related to vitamin B12 and homocysteine levels in children with ADHD. Further studies are required to define the role of these parameters and effects on the etiology and clinical manifestations of ASD and ADHD.

Relationship between serum zinc and homocysteine in children with nephrotic syndrome

Background In children, most idiopathic nephrotic syndrome (NS) is a minimal lesion, which responds well to steroids. Hyperhomocysteinemia is pathologic and worsens NS by causing chronic inflammation, leading to glomerular sclerosis. Zinc metalloenzymes are involved in homocysteine metabolism.&#x0D; Objective To assess for a possible relationship between serum zinc and homocysteine in children with NS.&#x0D; Methods A cross-sectional study was conducted in children with NS aged 1-18 years, who were admitted to Hasan Sadikin Hospital from November 2017 - January 2018. Subjects were selected consecutively. Serum zinc and homocysteine were measured in all subjects. Statistical analysis was done with Pearson’s correlation test. If the distribution was not linear, the analysis was continued with non-linear regression.&#x0D; Results There were 23 children who met the inclusion criteria. Mean serum homocysteine and zinc levels were 10.37 (SD 4.11) µmol/L and 51.13 (SD 29.69) µg/dL, respectively. Pearson’s correlation analysis showed no linear correlation between them (r coefficient -0.173; P=0.430). However, after adjusting for age and serum albumin level, multiple regression analysis suggested a cubical relationship between serum homocysteine and zinc, using the equation: homocysteine = -4.572 + 0.735 x zinc - 0.0012 x zinc2 + 0.00005 x zinc3 x age (months) (R2 multiple=53.2%; P=0.012). This equation indicates that 53.2% of homocysteine variation was influenced by serum zinc concentration.&#x0D; Conclusion In childhood NS, homocysteine is not correlated linearly with zinc, but related with cubical model.

Significance of homocysteine in the occurrence and development of pediatric diseases

Homocysteine is a metabolite of methionine, which has been proved to be associated with multiple systemic diseases.In pediatric diseases, homocysteinemia has been paid more and more attention in recent years.Hyperhomocysteinemia is associated with some diseases of cardiovascular system, rheumatoid immune system, urinary system, nervous system, blood system, digestive system in children.And early measurement of homocysteinemia plays an important role in the diagnosis, treatment and prevention of some diseases in children.Through sunmmarizing the metachanism of homocysteine and its relationship with multiple systemic diseases in children, we investigate the clinical value of homocysteine in children. Key words: Homocysteine; Hyperhomocysteinemia; Child; Clinical disease

Plasma Free Homocysteine Levels in Children with Idiopathic Nephrotic Syndrome.

Altered metabolism of homocysteine in children with idiopathic nephrotic syndrome leads to raised plasma-free homocysteine levels. Elevated free homocysteine causes endothelial cell dysfunction and promotes early atherosclerosis and glomerulosclerosis. In this analytical study with a longitudinal follow-up, 29 children with first episode of nephrotic syndrome (FENS) aged 1–16 years along with 30 age andgender-matched healthy controls were enrolled. Plasma-free homocysteine was measured using high-performance liquid chromatography (HPLC). Other variables were measured using standard biochemical methods. The primary outcome measure was plasma-free homocysteine level in children with FENS and in controls. The secondary outcome measure was to observe the levels of plasma-free homocysteine in children with FENS at 12 weeks in remission and in steroid resistant states. Plasma-free homocysteine levels were significantly elevated in children with FENS at disease onset [Median (IQR) 2.170 (1.54–2.71); N = 29; P < 0.001], at 12 weeks of steroid-induced remission [Median (IQR) 1.946 (1.53–2.71); N = 22; P < 0.001], and in steroid-resistant states [Median (IQR) 2.262 (1.53–2.74); N = 7; P < 0.001] compared to controls. The levels did not decrease significantly at 12 weeks of steroid-induced remission compared to onset of nephrotic syndrome. Plasma-free homocysteine levels correlated positively with serum total cholesterol (P = 0.005; r = 0.362) and negatively with serum albumin (P = 0.032; r = 0.281). Plasma-free homocysteine levels are raised in children with FENS posing a risk of endothelial dysfunction which persists at least in short term. Long-term effects of raised plasma-free homocysteine needs to be studied.

Homocysteine Level in Children with Classic Congenital Adrenal Hyperplasia: Relationship to Carotid Intimal Wall Thickness and Left Ventricular Function

Background/Aims: Homocysteine is an important and independent risk factor for atherosclerotic diseases. The aim of this study was to evaluate serum levels of homocysteine in children with congenital adrenal hyperplasia (CAH) and their relation to carotid artery intima-media thickness (CA-IMT) and left ventricular (LV) function. Methods: This study included 36 children with classic CAH and 36 healthy children. All underwent anthropometric evaluation. Measurement of serum levels of total homocysteine was carried out. The LV mass (LVM) and function were assessed using conventional echocardiography. Duplex ultrasonography was used to measure CA-IMT. Results: Compared to the controls, the patients had higher homocysteine levels (p = 0.001), a thicker CA-IMT (p = 0.01), a higher LVM index (LVMI) (p = 0.001), and a prolonged mitral deceleration time (DcT) (p = 0.01). Abnormalities were marked in children who were uncontrolled on medical treatment. In multivariate analysis, homocysteine levels were significantly correlated with systolic (OR = 2.2; 95% CI: 1.10–1.18; p = 0.01) and diastolic blood pressures (OR = 2.9; 95% CI: 1.45–2.4; p = 0.01), atherogenic index (OR = 2.6; 95% CI: 1.33–2.89; p = 0.01), HOMA-IR (OR = 1.3; 95% CI: 1.04–1.34; p = 0.001), LVMI (OR = 2.6; 95% CI: 1.1–1.13; p = 0.001), mitral DcT (OR = 2.4; 95% CI: 1.15–2.05; p = 0.01), and CA-IMT (OR = 1.6; 95% CI: 1.16–1.57; p = 0.01). Conclusions: Serum total homocysteine was elevated in children with classic CAH, particularly in those with poor control on medical treatment, and it was correlated with CA-IMT, LVMI, and mitral DcT. Measurement of homocysteine in children with CAH may help to identify those at high risk of developing LV dysfunction and subclinical atherosclerosis.

DIAGNOSTIC MEANING OF DETERMINATION OF HOMOCYSTEIN IN THE BLOOD SERUM IN CHILDREN WITH NEUROINFECTIONS

The aim of the study was to determine the serum level of homocysteine in children with neuroinfections. Mаterials and methods: A blood serum assay of 60 children with viral and bacterial neuroinfections was performed using the enzyme immunoassay to evaluate homocysteinemia as a marker of endothelial dysfunction. Results: In interpreting the results, the average level of hyperhomocysteinemia in patients with bacterial and viral neuroinfections was established. The highest homocysteine levels in serum were observed in bacterial neuroinfections, especially in the presence of signs of meningoencephalitis and pneumococcal etiology of the disease. Dependence of changes in the level of homocysteinemia from the sex of sick children was not revealed. Conclusion: Neuroinfections in children, regardless of the cause, are accompanied by hyperhomocysteinemia, indicating the presence of endothelial activation in this pathology, more pronounced in the case of a bacterial etiology of the infectious process and the combined lesion of the soft dura mater and the brain substance.

HOMOCYSTEINE LEVEL IN CHILDREN WITH CHRONIC KIDNEY DISEASE ON THE BACKGROUND OF CONGENITAL MALFORMATIONS OF THE URINARY SYSTEM

The aim: to evaluate diagnostic and prognostic value of determination the concentration of homocysteine in children with congenital malformations (CM) of the urinary system (US) dependent of kidneys functional state. Patients and methods. The study included 119 patients with US CM aged 3 to 18 years. A control group of 10 clinically healthy children. Patients divided into 3 groups: group I – 55 children with congenital vesicoureteral reflux (VUR), group II – 34 children with hydronephrosis and ureterohydronephrosis of congenital origin, group III – 30 children with other forms of US dysembryogenesis. Concentration of homocysteine in blood serum was assessed by ELISA. Results. Hyperhomocysteinemia diagnosed in 60,9% of cases. Statistically significant differences with control group were revealed in the obstructive types where more often arterial hypertension (AH) and reduced glomerular filtration rate (GFR) were diagnosed. Significantly higher concentration of homocysteine are registered in patients with hypertension and reduced GFR. Conclusion. The importance of estimating concentration of homocysteine in chronic kidney disease in patients with US CM was demonstrated.

The effects of antipsychotics on weight gain, weight-related hormones and homocysteine in children and adolescents: a 1-year follow-up study.

To analyze weight gain, metabolic hormones, and homocysteine (Hcys) levels in children and adolescents on antipsychotics (AP) during a year-long follow-up. 117 patients, AP-naïve or quasi-naïve (less than 30days on AP), were included. Weight, body mass index (BMI), BMI z-score (z-BMI), and levels of leptin, insulin, insulin resistance (HOMA-IR), adiponectin, ghrelin, thyroid stimulating hormone (TSH), free thyroxine (FT4), and Hcys were measured at baseline, and at 3, 6, and 12months, while patients remained on the same AP. Patients (mean age: 14.4±3years; 64.1% male) were on risperidone (N=84), olanzapine (N=20) or quetiapine (N=13) from baseline up to 1-year follow-up and significantly increased weight (5.8±4.3kg at 3-month, 8.1±6.1kg at 6-month, and 11.6±7.0kg at 1 year), BMI, and z-BMI. Leptin levels significantly increased from baseline to 3 and 6 months, as did TSH levels from baseline to 3 months, while FT4 levels decreased from baseline to 3 and 6 months. Patients with BMI>85th percentile at baseline (N=16) significantly increased weight, BMI, and z-BMI, more than patients with normal BMI over time. Higher baseline levels of insulin, HOMA-IR, and leptin were associated with increased weight/BMI during follow-up, while higher baseline levels of FT4, adiponectin, and ghrelin were associated with lower weight/BMI during follow-up. All AP were associated with increased weight and BMI/z-BMI in all of the assessments; however, at 1-year assessment, this increase was significantly higher for patients on quetiapine. Both higher baseline levels of insulin, HOMA-IR, and leptin, as well as being overweight/obese at baseline were associated with increased weight/BMI during 1-year follow-up in children and adolescents on AP. Awareness of weight-related parameters in this population may help inform decisions regarding AP prescriptions.

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.

Combined effect of folate and adiposity on homocysteine in children at three years of age

BACKGROUND/OBJECTIVESCardiovascular diseases is a major cause of death and is responsible for 23.8% of deaths in Korea. Clinical symptoms manifest in adulthood, but susceptibility begins in utero. Elevated homocysteine levels and adiposity might be linked to a greater risk in children as well as adults. We hypothesized that those who have simultaneous risk for folate and adiposity would be affected with elevated homocysteine levels at 3 years of age.SUBJECTS/METHODSFrom the ongoing birth cohort at Ewha Womans University Mok-Dong Hospital, we compared adiposity parameters, serum homocysteine, and folate levels in 238 children (118 boys and 120 girls) at three years of age. The relationship between birth outcome, current weight and body mass index (BMI), postnatal growth, and homocysteine level were assessed using correlation and general linear model. Additionally, we assessed the combined effect between blood folate status and adiposity on current homocysteine levels.RESULTS Birth characteristics were not correlated with homocysteine. Current weight, BMI, upper-arm circumference, skinfold thickness, waist circumference, and hip circumference were positively correlated with homocysteine at three years of age (P < 0.05). Folate level was negatively correlated with homocysteine at three years of age (P < 0.0001). A relative high anthropometric measure which is compatible with adiposity and low folate level was associated with high homocysteine levels.CONCLUSIONWe found a combined effect of adiposity and folate levels with homocysteine levels at three years of age. This implicates the beneficial role of folate supplementation in the high-risk population at an early age.

Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency

The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children aged 5 to 18 years with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB) or placebo with similar energy and fat content. Plasma amino acids were measured at baseline and 3 and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most participants. Alanine and cysteine were elevated in 24% and 36% of participants, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared with placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine, and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LYM-X-SORB did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI.

The hematological effects of nitrous oxide anesthesia in pediatric patients.

Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients. This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide-free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macrocytosis/microcytosis, anisocytosis, hyperchromatosis/hypochromatosis, thrombocytopenia, and leukopenia. The change (Δ) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW). No pancytopenia was present in any patient after surgery. All patients had postoperative anemia, and none had macrocytosis. Postoperative MCV (mean [99% confidence interval]) peaked at 86 fL (85-88 fL), 85 fL (81-89 fL), and 88 fL (80-96 fL) and postoperative RDW at 13.2% (12.8-13.5%), 13.3% (12.7-13.8%), and 13.0% (11.4-14.6%) for the maintenance group, the induction/emergence group, and the nitrous oxide-free group. Two patients in the maintenance group (5%) developed anisocytosis (RDW >14.6%), but none in the induction/emergence group or in the nitrous oxide-free group (P = 0.43). Both ΔMCV (P = 0.52) and ΔRDW (P = 0.16) were similar across all groups. Nitrous oxide exposure for up to 8 hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery.

Increased homocysteine levels correlate with the communication deficit in children with autism spectrum disorder

The clinical significance of high levels of homocysteine in autism spectrum disorder (ASD) is unknown. An experimental study was conducted in order to evaluate the concentration of homocysteine in children with ASD and typically developing children and to analyse any relationships with the severity of core symptoms of ASD and other clinical features (drugs, co-morbidities, gender, age, diet). Core symptoms of autism were evaluated by DSM-IV criteria. Homocysteine, glutathione, methionine, 3-nitrotyrosine were measured in urine. The increase in homocysteine concentration was significantly and directly correlated with the severity of the deficit in communication skills, but was unrelated to deficit in socialisation or repetitive/restricted behaviour. Urinary homocysteine concentration may be a possible biomarker for communication deficits in ASD and a potential diagnostic tool useful to evaluate new treatment options since no treatment for core symptoms of ASD are available.

Effect of anti epileptic therapy on serum homocysteine in children

Background: Elevated serum homocysteine concentration is associated with increased risk for vaso-occlusive disease like cerebrovascular stroke, coronary artery disease, and also the risk of resistance to anti-epileptics and refractory epilepsy. Hyperhomocysteinemia has been frequently associated with the administration of anti epileptic drugs (AEDs).

P42 – 1873 Effect of anti-epileptic therapy on serum homocysteine in children

P42 – 1873 Effect of anti-epileptic therapy on serum homocysteine in children

Notorious Oxide

Notorious Oxide