total homocysteine
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2022 ◽  
Vol 23 (2) ◽  
pp. 928
Author(s):  
Isao Ishii ◽  
Shotaro Kamata ◽  
Saki Ito ◽  
Aya Shimonaga ◽  
Maika Koizumi ◽  
...  

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×–13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.


Author(s):  
Akshunna Keerti ◽  
Jayshri Jankar

The metabolic condition known as diabetes mellitus is marked by hyperglycemia, a host of symptoms affecting the heart, kidneys, nerves, and other organs. Diabetes nephropathy is one of the leading causes of diabetic impermanence and morbid state. Low parameters of pteroylglutamic acid in the blood are associated with Diabetic Nephropathy, whereas endothelial dysfunction increases the risk for T2D. Endothelial dysfunction is associated with diabetes, which perhaps is caused by the disjunction of the endothelial nitric oxide (NO) synthase enzyme, which reduces NO availability. Because folic acid can repair the disjunction of NO synthase, we sought to see if pteroylglutamic acid supplementation may affect the function of the endothelial layer and inflammatory indicators in type 2 diabetes patients who did not have vascular disease. Recent studies have shown that pteroylglutamic acid also has direct benefits on the function of endo, in addition to its natural function of lowering homocysteine. Folic acid might serve as a "biomarker" for the function of endothelial cells. Many mechanisms have been linked to higher total homocysteine levels and type 2 diabetes risk in diabetic patients. Higher folic acid levels altered endothelial-dependent vasodilation in T2D patients. In patients with coronary heart disease (CAD), folic acid supplementation has been found to reduce homocysteine parameters and improve the function of the endothelial layer. On the other hand, RCTs looking at IR and T2D outcomes have shown mixed results. Several mechanisms link higher total homocysteine levels to increased risk of insulin resistance (IR) and type 2 diabetes mellitus (T2D). Treatment with folate has been shown to bring down homocysteine parameters and improve the endothelium functions in people with coronary heart disease (CAD). Randomized controlled trials (RCTs) on IR and T2D outcomes, on the other hand, have produced a wide range of results.


2021 ◽  
Vol 13 ◽  
Author(s):  
Guili Zhang ◽  
Shuai Liu ◽  
Zhichao Chen ◽  
Zhihong Shi ◽  
Wenzheng Hu ◽  
...  

Background: Elevated plasma total homocysteine (tHcy) level, a known risk factor for vascular disease, is reported to be an independent risk factor for cognitive impairment and Alzheimer’s disease (AD) in most studies. tHcy may also be associated with dementia with Lewy bodies (DLB).Objective: To investigate the association between plasma tHcy levels and DLB or AD.Methods: This is a case-control study including 132 DLB patients, 264 AD patients, and 295 age-matched healthy controls. We used multivariate logistic regression model to analyze the data with adjustments for confounding variables.Results: The highest tHcy tertile (>13.9 μmol/L) was significantly independently associated with DLB [adjusted odds ratio (OR): 4.65, 95% confidence interval (CI): 1.95–11.10, P = 0.001] and AD (adjusted OR: 1.82, 95% CI: 1.02–3.23, P = 0.041) compared to the lowest tertile (<10.7 μmol/L). The cumulative frequency plots showed a shift in the distribution of the tHcy concentrations to higher values in patients with DLB compared to AD. The mean tHcy levels were stable and not altered by the duration of cognitive impairment prior to the collection of blood samples from DLB patients.Conclusion: Elevated plasma tHcy levels were independently associated with DLB, and the association was stronger for DLB than for AD. The lack of a relationship between tHcy levels and symptom duration may refute these observed associations being a consequence of DLB, and future longitudinal studies will be required to confirm whether tHcy plays a causative role in DLB.


Author(s):  
VINOD KUMAR MEHTA ◽  
ABHIJIT BASU ◽  
PRAHARSH H PATHAK ◽  
AYUSHI JAIN ◽  
NEHA SHARMA

Objective: Till date, a very few prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Indian populations. Methods: A prospective, case - control study of Indian subjects 10–90 years of age was conducted using frozen serum samples from 103 participants in cardiovascular risk surveys collected from December 2017 to November 2018. By the end of 103, we identified 55 incidents of severe strokes, one control subject per case was selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by Cobas c-311. Results: Compared with control subjects, total (n_206), hemorrhagic (n_106), and ischemic (n_87) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine −25.0 μ mol/L. Homocysteine was estimated after adjustment for body mass index, smoking, alcohol intake, hypertension, and other cardiovascular risk factors. The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusion: High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke) Capsuloganglionic and frontoparietal infarct (8 each)., among Indian men and women.


Author(s):  
Roshan Iqbal ◽  
S. Harsha ◽  
Nemichandra S. C. ◽  
Shasthara Paneyala ◽  
Vimala C. Colaco

Background: The prevalence of dementia is increasing worldwide and with India experiencing an epidemiological transition with increasing ageing population, the prevalence in India is expected to double by 2030 adding to the already high burden of significant health care costs and caregiver fatigue. Indian population has a higher burden of elevated homocysteine levels due to multiple factors. However, studies correlating the homocysteine levels and severity of dementia in the Indian subcontinent is lacking. This study is aimed to analyse the diagnostic utility of serum total homocysteine in dementia and to examine the association between serum total homocysteine levels and severity of dementia.Methods: This was a cross-sectional hospital-based study on patients attending neurology out-patient department who satisfied the DSM-V criteria. Each participant underwent an interview of general health and function followed by a standard assessment including medical history, physical and neurological examination as well as a neuropsychological battery.Results: A total of 30 patients fulfilling the DSM-Vcriteria for Dementia were included in the study. Increasing S. Homocysteine levels were associated with lower neuropsychological compound scores with MMSE score of 20.78±2.98 and ACE-3 score of 77.40±5.60 in patients with Serum Homocysteine less than 22 Umoles/L and 18.85±2.50 and 75.55±5.06 respectively in patients with serum homocysteine levels above 22 Umoles/L. However, there was no statistically significant correlation between neurocognitive scores and serum homocysteine levels (p value 0.06 for MMSE and 0.19 for ACE-3). Also, no correlation was found between severity of dementia and serum homocysteine levels with p≥0.05 and Pearson’s correlation coefficient r=0.06.Conclusions: This study shows no significant association between serum total homocysteine levels and severity of dementia. Thus, the association of homocysteine as an independent risk factor with the diagnosis and severity of dementia needs to be re-evaluated as it might undermine the multiple mechanisms underlying the pathogenesis of dementia.


2021 ◽  
Vol 7 (3) ◽  
pp. 48
Author(s):  
Alexander Asamoah ◽  
Sainan Wei ◽  
Kelly E. Jackson ◽  
Joseph H. Hersh ◽  
Harvey Levy

Homocystinuria, caused by cystathionine β-synthase deficiency, is a rare inherited disorder involving metabolism of methionine. Impaired synthesis of cystathionine leads to accumulation of homocysteine that affects several organ systems leading to abnormalities in the skeletal, cardiovascular, ophthalmic and central nervous systems. We report a 14-month-old and a 7-year-old boy who presented with neurologic dysfunction and were found to have cerebral venous sinus thromboses on brain magnetic resonance imaging (MRI)/magnetic resonance venogram (MRV) and metabolic and hypercoagulable work-up were consistent with classic homocystinuria. The 14-month-old boy had normal newborn screening. The 7-year-old boy initially had an abnormal newborn screen for homocystinuria but second tier test that consisted of total homocysteine was normal, so his newborn screen was reported as normal. With the advent of expanded newborn screening many treatable metabolic disorders are detected before affected infants and children become symptomatic. Methionine is the primary target in newborn screening for homocystinuria and total homocysteine is a secondary target. Screening is usually performed after 24–48 h of life in most states in the US and some states perform a second screen as a policy on all tested newborns or based on when the initial newborn screen was performed. This is done in hopes of detecting infants who may have been missed on their first screen. In the United Kingdom, NBS using dried blood spot is performed at 5 to 8 days after birth. It is universally known that methionine is a poor target and newborn screening laboratories have used different cutoffs for a positive screen. Reducing the methionine cutoff increases the sensitivity but not necessarily the specificity of the test and increasing the cutoff will miss babies who may have HCU whose levels may not be high enough to be detected at their age of ascertainment. It is not clear whether adjusting methionine level to decrease the false negative rates combined with total homocysteine as a second-tier test can be used effectively and feasibly to detect newborns with HCU. Between December 2005 and December 2020, 827,083 newborns were screened in Kentucky by MS/MS. Kentucky NBS program uses the postanalytical tools offered by the Collaborative Laboratory Integrated Reports (CLIR) project which considers gestational age and birthweight. One case of classical homocystinuria was detected and two were missed on first and second tier tests respectively. The newborn that had confirmed classical homocystinuria was one of twenty-three newborns that were referred for second tier test because of elevated methionine (cutoff is >60 µmol/L) and/or Met/Phe ratio (cutoff is >1.0); all 23 dried blood spots had elevated total homocysteine. One of the subjects of this case report had a normal methionine on initial screen and the other had a normal second-tier total homocysteine level. The performance of methionine and total homocysteine as screening analytes for homocystinuria suggest that it may be time for newborn screening programs to consider adopting next generation sequencing (NGS) platforms as alternate modality of metabolic newborn screening. Because of cost considerations, newborn screening programs may not want to adopt NGS, but the downstream healthcare cost incurred due to missed cases and the associated morbidity of affected persons far exceed costs to newborn screen programs. Since NGS is becoming more widely available and inexpensive, it may be feasible to change testing algorithms to use Newborn Metabolic NGS as the primary mode of testing on dry blood specimens with confirmation with biochemical testing. Some commercial laboratories have Newborn Screening Metabolic gene panel that includes all metabolic disorders on the most comprehensive newborn screening panel in addition to many other conditions that are not on the panel. A more targeted NGS panel can be designed that may not cost much and eventually help avoid the pitfalls associated with delayed diagnosis and cost of screening.


2021 ◽  
Vol 7 (3) ◽  
pp. 39
Author(s):  
Reiko Kagawa ◽  
Go Tajima ◽  
Takako Maeda ◽  
Fumiaki Sakura ◽  
Akari Nakamura-Utsunomiya ◽  
...  

Neonatal screening (NS) for methylmalonic acidemia uses propionylcarnitine (C3) as a primary index, which is insufficiently sensitive at detecting methylmalonic acidemia caused by defects in the adenosylcobalamin synthesis pathway. Moreover, homocystinuria from cystathionine β-synthase deficiency is screened by detecting hypermethioninemia, but methionine levels decrease in homocystinuria caused by defects in homocysteine remethylation. To establish NS detection of methylmalonic acidemia and homocystinuria of these subtypes, we evaluated the utility of indices (1) C3 ≥ 3.6 μmol/L and C3/acetylcarnitine (C2) ≥ 0.23, (2) C3/methionine ≥ 0.25, and (3) methionine < 10 μmol/L, by retrospectively applying them to NS data of 59,207 newborns. We found positive results in 116 subjects for index (1), 37 for (2), and 15 for (3). Second-tier tests revealed that for index 1, methylmalonate (MMA) was elevated in two cases, and MMA and total homocysteine (tHcy) were elevated in two cases; for index 2 that MMA was elevated in one case; and for index 3 that tHcy was elevated in one case. Though data were anonymized, two cases identified by index 1 had been diagnosed with maternal vitamin B12 deficiency during NS. Methylene tetrahydrofolate reductase deficiency was confirmed for the case identified by index 3, which was examined because an elder sibling was affected by the same disease. Based on these data, a prospective NS study is underway.


2021 ◽  
Vol 19 (02) ◽  
pp. 22-28
Author(s):  
AFFANDI OMAR ◽  
SITI ROZILAH ABDUL KADIR ◽  
SALINA ABDUL RAHMAN ◽  
FATIMAH DIANA AMIN NORDIN ◽  
BALQIS KAMARUDIN ◽  
...  

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