Elevated Serum Homocysteine Levels Research Articles

Elevated serum homocysteine levels associated with poor recurrence-free and overall survival in patients with colorectal cancer

This study aimed to evaluate the significance of homocysteine (HCY) levels in predicting recurrence-free survival (RFS) and overall survival (OS) in colorectal cancer (CRC) patients. This retrospective study involved 1272 CRC patients. The risk of mortality increased with increasing HCY levels in CRC patients. The optimal HCY cutoff value in CRC patients was 15.2 μmol/L. The RFS (45.8% vs. 60.5%, p < 0.001) and OS (48.2% vs. 63.2%, p < 0.001) of patients with high HCY levels were significantly lower than those of patients with low HCY levels. Patients with high HCY levels were older, male, had large tumours, high carcinoembryonic antigen (CEA) levels, and long hospital stays, and incurred high hospitalisation costs. Multivariate analysis showed that when HCY levels exceeded 15.2 μmol/L, the risk of adverse RFS and OS increased by 55.7% and 61.4%, respectively. Subgroup analysis showed that HCY levels could supplement CEA levels and pathological staging. We constructed HCY-based prognostic nomograms, which demonstrated feasible discrimination and calibration values better than the traditional tumour, node, metastasis staging system for predicting RFS and OS. Elevated serum HCY levels were strongly associated with poor RFS and OS in CRC patients. HCY-based prognostic models are effective tools for a comprehensive evaluation of prognosis.

Homocysteine-potentiated Kelch-like ECH-associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of β-catenin.

Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated β-catenin and Kelch-like ECH-associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the β-catenin-WTX interaction. Mechanistically, Hcy attenuated the methylation level of the KEAP1 promoter CpG island and activated KEAP1 transcription. However, a slow degradation rate rather than transcriptional activation contributed to the high level of β-catenin. Hcy-upregulated KEAP1 competed with β-catenin to bind to WTX. Knockdown of both β-catenin and KEAP1 attenuated Hcy-induced senescence in N2a cells. Our data highlight a crucial role of the KEAP1-β-catenin pathway in Hcy-induced neuronal-like senescence and uncover a promising target for AD treatment.

Combined central retinal vein occlusion and cilioretinal artery occlusion in an MTHFR C677T homozygous 26-year-old patient with hyperhomocysteinemia: Case report

A 26-year-old female patient presented with sudden, painless visual disturbances in her right eye (RE). Fundus examination revealed signs of a central retinal vein occlusion (CRVO) (hemorrhages, mild venous tortuosity, mild disc swelling, and blurred disc margins), as well as a white ischemic area nasal to the optic nerve, suggesting a possible cilioretinal artery occlusion (CLRAO). A diagnosis of combined CRVO and nasal CLRAO with homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and elevated levels of serum homocysteine was made. The patient was prescribed folic and acetylsalicylic acid and subsequent follow-up demonstrated gradual improvement.

Hyperhomocysteinemia Increases Vascular Risk in Stroke Patients with Chronic Kidney Disease.

We aimed to assess the prognostic impact of hyperhomocysteinemia (HHcy) on the recurrent vascular event risk in stroke patients with or without chronic kidney disease (CKD). In this prospective observational study, 621 patients (mean age, 69.5 years; male, 62.2%) with ischemic stroke or transient ischemic attack were consecutively enrolled within 1 week of onset and followed-up for 1 year. HHcy was defined as elevated levels of fasting total homocysteine ＞15 µmol/L. CKD was defined as an estimated glomerular filtration rate of ＜60 mL/min/1.73 m2 or a history of renal replacement therapy. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including nonfatal stroke, nonfatal acute coronary syndrome, major peripheral artery disease, and vascular death. The prevalence of HHcy was 18.5%. Patients with HHcy were more likely to have intracranial (37.4% versus 24.8%; p=0.008) and extracranial (20.9% versus 13.0%; p=0.037) artery stenosis than were those without HHcy. At 1 year, patients with HHcy were at a greater risk of MACE than were those without HHcy (annual rate, 17.8% versus 10.4%; log-rank p=0.033). In the Cox proportional hazard regression models, HHcy was independently associated with an increased risk of MACE in patients with CKD (adjusted hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.02-4.20), whereas HHcy was not predictive of MACE in those without CKD (adjusted HR, 1.00; 95% CI, 0.30-3.32). Elevated levels of serum homocysteine can be an important modifiable risk factor in stroke patients with CKD, but not in those without CKD.

Lesion location and serum levels of homocysteine are associated with early-onset post-stroke depression in acute ischemic stroke.

It is well known that post-stroke depression (PSD) is a psychiatric complication after stroke which leads to worse functional outcome and poorer quality of life. Some risk factors including gender, stroke severity, lesion location, homocysteine (HCY), and so on are associated with PSD. This study aims to further explore the possible relationship between serum levels of HCY and early-onset PSD and the predictive value of HCY combined with stroke characteristics for early-onset PSD. Two hundred forty-five patients with acute ischemic stroke who met the criteria were included in this study from March 2015 to March 2017. PSD was diagnosed at 2weeks after stroke. The severity of depressive symptoms was evaluated with the Hamilton depression scale 17 items (HAMD-17), and patients with HAMD scores ≥7 were included in the PSD group. The demographic data, clinical characteristics, serum levels of HCY, and detailed radiological variables (e.g., lesion location and quantity of the brain infarct) were also examined. In total, 97 (39.6%) patients of the 245 patients were diagnosed with depression. The univariate analyses suggested that patients in PSD group had a higher NIHSS score, modified Rankin Scale score, and HCY levels than patients in non-PSD group (p < .001). The patients with PSD had higher proportion of multiple-site acute infarcts and frontal lobe lesion (p < .05). In multivariate logistic regression analysis, NIHSS score at admission, serum levels of HCY, and multiple-site lesions were independently related to early-onset PSD. Based on receiver operating characteristic curves analysis, the combination of HCY, NIHSS scores, multiple-site lesions, and lesion location revealed a highest area under the curve of 0.807 (95% confidence interval [CI]: 0.748-0.865, p < .001). Furthermore, there was a significantly increased risk of early-onset PSD associated with serum levels of HCY ≥16.98μmol/L (odds ratio [OR]=10.976, 95% CI: 5.585-21.573, p < .001). Our study indicated that higher NIHSS score, elevated serum levels of HCY, and multiple-site lesions may be independent risk factors of early-onset PSD. The combination of HCY, NIHSS scores, multiple-site lesions, and lesion location may provide greater predictive value than HCY alone for early-onset PSD. Early intervention for elevated serum levels of HCY may be a potential target for the intervention and prevention of PSD.

An orally administered enzyme therapeutic for homocystinuria that suppresses homocysteine by metabolizing methionine in the gastrointestinal tract.

Classical homocystinuria (HCU) is a rare inborn error of amino acid metabolism characterized by accumulation of homocysteine, an intermediate product of methionine metabolism, leading to significant systemic toxicities, particularly within the vascular, skeletal, and ocular systems. Most patients require lifelong dietary therapy with severe restriction of natural protein to minimize methionine intake, and many patients still struggle to maintain healthy homocysteine levels. Since eliminating methionine from the diet reduces homocysteine levels, we hypothesized that an enzyme that can degrade methionine within the gastrointestinal (GI) tract could help HCU patients maintain healthy levels while easing natural protein restrictions. We describe the preclinical development of CDX-6512, a methionine gamma lyase (MGL) enzyme that was engineered for stability and activity within the GI tract for oral administration to locally degrade methionine. CDX-6512 is stable to low pH and intestinal proteases, enabling it to survive the harsh GI environment without enteric coating and to degrade methionine freed from dietary protein within the small intestine. Administering CDX-6512 to healthy non-human primates following a high protein meal led to a dose-dependent suppression of plasma methionine. In Tg-I278T Cbs-/- mice, an animal model that recapitulates aspects of HCU disease including highly elevated serum homocysteine levels, oral dosing of CDX-6512 after a high protein meal led to suppression in serum levels of both methionine and homocysteine. When animals received a daily dose of CDX-6512 with a high protein meal for two weeks, the Tg-I278T Cbs-/- mice maintained baseline homocysteine levels, whereas homocysteine levels in untreated animals increased by 39%. These preclinical data demonstrate the potential of CDX-6512 as an oral enzyme therapy for HCU.

Association of Elevated Serum Homocysteine Level in Women with Gestational Diabetes Mellitus

Background: In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Therefore, universal screening is widely recommended. Homocysteine levels during pregnancy in women with GDM have been studied; however, it remains unclear whether hyperhomocysteinemia is a useful predictor of GDM. Objective: To determine the association of serum homocysteine level in women with gestational diabetes mellitus. Methods: Case control study was conducted in the Department of Obstetrics and Gynaecology, Institute of Child and Mother Health (ICMH), Dhaka. Pregnant women in their 24 weeks to 40 weeks of gestation attended for antenatal care diagnosed as GDM was selected as cases. Non- diabetic pregnant women matching with cases by age and gestational age were selected as control in this study. GDM was diagnosed by oral glucose tolerance test (OGTT). The serum homocysteine level of these patients was measured. Descriptive and inferential analysis was carried out using SPSS version 22.0. P-value less than 0.05 will be considered as statistically significant. Results: Among the cases fasting blood sugar (6.13 ± 0.66) and controls (4.60 ± 0.57). Similarly, 2 hours after 75 gm. glucose blood sugar among cases (8.46 ± 0.88) and controls (6.32 ± 0.96). Both results were statistically significant p=0.001. Majority of patients were at third trimester of pregnancy (67.0%). 37.5% were primigravida and 2.5% were multigravida. Mean gestational age of cases (30.25 ± 2.74) and controls (30.02 ± 3.03). Among the cases 62.1% had history of GDM where 37.9% don’t have history of GDM. Among control group only 7.7% had history of GDM. This result statistically significant p=0.001. 6.9% cases had history of macrocosmic child which was not statistically significant p=0.49. There was no history of still birth or other congenital defect. Mean serum homocysteine level among cases (6.50 ± 1.72) and controls (5.20 ± 1.87) which was statistically significant p=0.001. Positive correlation observed between maternal serum homocysteine level and maternal blood sugar (r=0.209, p=0.005) in this study. Respondents with high homocysteine level have 3.94 times more chance to develop GDM (OR=3.94; 95% CI = 1.59-9.77). Conclusion: Finding from the present study suggests that maternal elevated serum homocysteine level in pregnancy is significantly associated with Gestational Diabetes Mellitus.

Elevated serum Homocysteine levels a possible non-invasive diagnostic biomarker in patients with Non-alcoholic fatty liver disease

Lack of independent biomarkers is very much evident in NAFLD. Early detection of NAFLD is difficult due to the absence of specific diagnostic and prognostic markers and clinical symptoms. We retrospectively collected the information of patients hospitalised with NAFLD diagnosis and metabolic syndrome during 2019-2020 using the tertiary care hospital inpatient sample database and evaluated the changes in their serum homocysteine levels. We found that 59.063% of NAFLD in the male population and 41.667% of NAFLD in the female population had increased serum homocysteine. This shows that elevated serum homocysteine can act as a potential biomarker for NAFLD.

Abstract Number ‐ 77: A Large Vessel Occlusion in Short Gut Syndrome‐ An Acquired Catastrophe of Hyper‐Homocysteinemia

Introduction Strokes secondary to large vessel occlusions (LVO) are frequently caused by either atherosclerotic or thromboembolic sources (1). Both genetic and acquired etiologies can lead to elevated serum homocysteine levels causing LVO as recognized in our patient (2). Measuring homocysteine levels and vitamin B12, B6, and folate replacement can reduce the future risk of stroke by ∼25% (3). Methods A 42‐year‐old male with acute onset right‐sided facial droop, ataxia, gait instability, nausea, and vomiting. PMH: 11 weeks preterm with subtotal colectomy and short gut syndrome, and mild hypertension. No family h/o blood clots. LKW: &gt;24 hours, initial NIHSS 6, required rapid sequence intubation with repeat NIHSS 28, decreased responsiveness, non‐reactive pupils, and ventilatory compromise. PE: decreased arousal and depressed mentation, facial asymmetry, flaccid right upper and lower extremity. Results Non‐contrast head CT: a hyperdense basilar artery (fig 1). CT angiogram of head and neck: Left vertebral artery stenosis with diminutive basilar artery. A diagnostic cerebral angiogram with mechanical thrombectomy was performed with TICI 2b recanalization (fig 2). A subsequent MRI brain further confirmed an acute bi‐cerebellar and left pontine ischemic infarct with diffusion restriction on DWI and ADC reversal (fig 1). Lab work: B12 &lt; 50, homocysteine 50.08, methylmalonic acid 38,038, and folate wnl. A transthoracic, transesophageal ECHO with bubble study and a lower extremity doppler ruled out peripheral sources of stroke. He developed malignant cerebral edema requiring decompressive sub‐occipital craniectomy with external ventricular drain (EVD) placement and remained in the Neuro ICU until discharge. Conclusions •A build‐up of hcy (an intermediate product of methionine and cysteine metabolism) can occur de novo via or iatrogenically •This can cause arterial occlusion leading to ischemic strokes and venous thrombosis as seen in our patient. •Serial monitoring of Hcy, MMA, and replacing the deficient vitamins like B12, B6, and folate in these patients can help prevent the chance of ischemic CNS injuries

High Homocysteine Levels During Pregnancy and Its Association With Placenta-Mediated Complications: A Scoping Review.

There is already abundant corroboration indicating that elevated serum homocysteine levels may be related to the risk of coronary, cerebral, and peripheral arterial diseases. High homocysteine levels have often been associated with placental vasculopathies and complications related to the placenta, such as fetal growth restriction, Abruption, hypertensive disorders of pregnancy, and recurrent abortions. This scoping review aims to integrate the currently available scientific literature and fill the gaps in our understanding of homocysteine metabolism during pregnancy and its relationship to placenta-mediated complications. Moreover, to summarize the existing literature on the correlation between raised maternal homocysteine levels in early gestation and its association with placenta-mediated complications. We developed this scoping review article by performing a literature review as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelinesand the search was conducted using PRISMA-S (an extension to PRISMA focusing on reporting the search components of systematic reviews) guidelines. The research question was clarified and modified using keywords with important literature published online between 2010 and 2022, which were included from PubMed, and Google Scholar databases with recognized titles and abstracts were examined and cross-checked for case overlap to choose the original reports. A summary of the descriptive data was organized according to the clinical manifestations (symptoms, imaging, and laboratory results) and outcomes (maternal and perinatal). In conclusion, a review of research papers from 2010 to 2022 showed that homocysteine levels during pregnancy fluctuate and are probably influenced by a population's regional, cultural, and socioeconomic status. According to the data, there is an association between elevated homocysteine levels and complications of pregnancies, such as early spontaneous abortions, pre-eclampsia, fetal development restriction, and abruption, as well as in certain cases of maternal and fetal mortality.

EPIDEMIC OF CAD IN YOUNG INDIANS : THE ACCELERATED ATHEROSCLEROTIC INSULIN RESISTANCE SYNDROME (AAIRS)

Introduction: CAD is the leading cause of mortality in India. It affects Indians atleast a decade early compared to the western population. Other than the conventional risk factors, the prevalence of other risk factors like hyperhomocystenemia, lipoprotein(a), metabolic syndrome, insulin resistance and fatty liver was studied in a large registry of documented CAD in patients. To study the prevalence of insulin resi Objectives: stance syndrome and its association with NAFLD, lipoprotein (a) and homocysteine levels in young Indian patients who present with coronary artery disease It is a single centre prospective sub study of the PCAD . Materials and Methods: (Premature coronary artery disease) registry cohort at Jayadeva Institute. : 344 patients and Results 300 controls were studied. The mean age was 32 years. There were 45 females and 299 males in cases, 99 females and 201 males in control group. Smoking was seen in 138 cases compared to 16 controls which was disproportionately high in the cases group. 8% of cases had diabetes whereas only 1.6% of controls had diabetes. 10% of cases had positive family history of CAD compared to 0 in control group. 68% of cases had metabolic syndrome whereas 36% of controls had metabolic syndrome. Elevated serum homocysteine levels were seen in 49 when compared to 46 controls which was statistically signicant. (p &lt;0.001). Homocysteine level more than 15 was seen in 68% of cases compared to 45% in controls which was statistically signicant.Serum lipoprotein a levels was signicantly higher in cases (mean of 52) compared to controls (mean of 26). Lp(a) level more than 30 was seen in 51% of cases compared to 27% of controls. HOMA IR was signicantly high in the cases group when compared to controls which was statistically signicant. Fatty liver grade 0 was seen in 25% of cases compared to 58% in controls. Fatty liver grade 1 was seen in 59% of cases compared to 37% in controls. Fatty liver grade 2 was seen in 15% of cases compared to 3.7% in controls, all were statistically signicant. Novel syndrome of AAIRS Conclusion: incorporating insulin resistance, NAFLD, Lipoprotein a and homocysteine was found to be statistically different between cases and controls. Hence, this can be used to predict the risk of premature coronary disease in young Indians To Aims: formulate a novel clinical syndrome titled Accelerated Atherosclerosis Insulin Resistance Syndrome (AAIRS) which will help to predict the risk of premature coronary heart disease in young Indians To study the prevalence of i Objectives: nsulin resistance syndrome and its association with NAFLD, lipoprotein (a) and homocysteine levels in young Indian patients who present with coronary artery disease

Is Maternal Serum Homocysteine a Novel Diagnostic Biomarker for Predicting Placenta-Mediated Disorders?

Background Uteroplacental insufficiency and related disorders, though a significant cause of undesirable maternal and fetal outcomes, are complex and poorly understood. The newer screening modalities are expensive and difficult to procure for day-to-day use in developing countries. This study aimed to examine the association of mid-trimester maternal serum homocysteine levels with maternal and neonatal outcomes. Methodology This was a prospective cohort study involving 100 participants between 18 and 28 weeks of gestation. The study was conducted at a tertiary care center in south India from July2019 to September 2020. Maternal blood samples wereanalyzed for serum homocysteine levels and correlated with the third-trimester pregnancy outcomes. Statistical analysis was done, and diagnostic measures were computed. Results The mean age was found to be 26.8 ± 4.8 years. Of the participants, 15% (n = 15) were diagnosed with hypertensive disorders during pregnancy, while 7% (n = 7) had fetal growth restriction (FGR) and 7% (n = 7) were complicated by preterm birth. An elevated maternal serum homocysteine level was positively associated with adverse pregnancy outcome measures such as hypertensive disorders (p = 0.001), with sensitivity and specificity of 27% and 99%, respectively, and FGR (p = 0.03) with sensitivity and specificity of 28.6% and 98.6%, respectively. Moreover, a statistically significant outcome was noted with preterm birth before 37 weeks (p = 0.001) and a low Apgar score (p = 0.02). No association was established with spontaneous preterm labor (p = 1.00), neonatal birth weight (p = 0.42), and special care unit admission (p = 1.00). Conclusions Such a simple and affordable investigation has the potential to go a long way in the early diagnosis and management of placenta-mediated disorders in pregnancy during the antenatal period, especially in low-resource settings.

Serum Homocysteine Levels in Indian Children on Valproate Monotherapy

Introduction: Various research works have reported elevated serum homocysteine levels with the use of antiepileptic drugs. This may lead to an increased risk of atherosclerosis, a higher seizure frequency and may also cause cognitive decline. Methods: Twenty five children (Two to 12 years) on valproate monotherapy for more than one year and the same number of age and sex-matched healthy controls were enrolled. Venous blood samples were analyzed for serum homocysteine, vitamin B12 and folic acid levels. All biochemical parameters were compared between the groups. Results: The antiepileptic drug users had significantly lower serum homocysteine levels and higher B12 levels as compared to the controls. But serum folate levels were similar between the groups. No correlation of serum homocysteine levels was observed with either serum folate, B12 or valproate. Conclusions: The use of valproate monotherapy for epilepsy in the Indian paediatric population does not increase the risk of hyperhomocysteinemia.

Saddle pulmonary embolus in a young man with homocysteinemia

Acute pulmonary embolism (PE) is a life-threatening condition, requiring immediate management. This case report summarises the evaluation and management of a patient who presented with a saddle pulmonary embolus. Since the patient had features suggestive of significant right heart dysfunction, he was thrombolysed with streptokinase but developed cardiogenic shock while on the streptokinase infusion. Therefore, catheter fragmentation and thrombectomy was performed with a view to break and remove the clot. Despite this, his condition deteriorated and unfortunately he died in the ICU. The thrombophilia screen sent before death showed significantly elevated serum levels of homocysteine, which could potentially have caused a hypercoagulable state. This case re-emphasises the mortality associated with major PE and the need for a detailed thrombophilia screen in patients with deep vein thrombosis or PE without any major clinical risk factors.

Proton pump inhibitor use and its effect on vitamin B12 and homocysteine levels among men and women: A large cross-sectional study.

Previous studies have demonstrated an association between proton pump inhibitors (PPI) use and vitamin B12 deficiency. However, data regarding PPI use and elevated serum homocysteine level, an important marker of vitamin B12 deficiency, are scant. Data were collected from medical records of subjects examined at a screening center in Israel. Cross sectional analysis was conducted on 25,953 subjects. Levels of vitamin B12 and homocysteine were compared between subjects who consumed PPI medications and those who did not. The mean age of the study population was 45 years and 33% were females. Subjects who received PPI medications had a minor higher vitamin B12 levels (320 pmol/L vs 300 pmol/L, p=0.024). Levels of vitamin B12 remained higher in females receiving PPI medications after performing a stratified analysis according to subjects' gender. Homocysteine levels were higher in subjects receiving PPI medications as compared to those who did not (12.0 μmol/L vs 11.6 0 μmol/L, p<0.001). Levels remained higher in female subjects after performing a stratified analysis according to subjects' sex. There was no statistically significant difference in the prevalence of vitamin B12 deficiency (according to two cutoffs: vitamin B12≤200 or ≤140 pmol/L) as well as the prevalence of hyperhomocysteinemia (defined as homocysteine >15.0 μmol/L) between the two groups. According to our study, no association was found between PPI medication use and vitamin B12 deficiency or hyperhomocysteinemia. Patients receiving PPI medications had slightly higher levels of vitamin B12 and homocysteine, however these differences were too small to have any clinical relevance.

Identification of MMACHC and ZEB2 mutations causing coexistent cobalamin C disease and Mowat-Wilson syndrome in a 2-year-old girl

Cobalamin C (cblC) disease and Mowat-Wilson syndrome (MWS) are rare hereditary diseases. To date, there have been no reports of people suffering from these two genetic diseases, or whether there is any correlation between the two diseases. We reported a 2-year-old girl with both cblC disease and MWS. The patient initially manifested as slow weight gain, hypotonia, broad nasal bridge, high forehead, high palate arch, ear crease, patent ductus arteriosus, atrial and ventricular septal defect and bilateral mild ventriculomegaly in the neonatal period. However, as the baby grew older, the typical facial features became more prominent, and overall developmental delays were noted at the subsequent follow-up, with the motor and cognitive development significantly lagging behind that of other children of the same age. At 26 days old, laboratory tests revealed remarkably elevated levels of serum homocysteine, C3/C2 and urine organic acid. Whole-exome sequencing detected compound heterozygous variants in MMACHC, including one previously reported mutation [c.609G > A (p.W203X) and a novel missense mutation[ c.643 T > C (p.Y215H)]. The computer simulations of the protein structure analysis of the novel missense mutation showed the variant p.Y215H replaced a neutral amino acid with a strongly basic lysine, which broken the local structure by changing the carbon chain skeleton and decreasing the interaction with adjacent amino acid. This is expected to damage the utilization of vitamin B12 and influence the synthesis of AdoCbl and MeCbl, contributing to its pathogenicity. Thus, clinical and genetic examinations confirmed the cblC disease. Another heterozygous variant in ZEB2 [NM_014795; loss1(exon:2–10)(all); 127901 bp] was detected by whole-exome sequencing. The heterozygous 3.04 Mb deletion in EB2 [GRCH37]del(2)(q22.2q22.3) (chr2:142237964–145274917) was also confirmed by genome-wide copy number variations (CNVs) scan, which was pathogenic and led to the diagnosis of Mowat-Wilson syndrome. The biochemical indicators associated with cblC disease in the patient were well controlled after treatment with vitamin B12 and betaine. Here, a patient with coexisting cblC disease and MWS caused by different pathogenic genes was reported, which enriched the clinical research on these two rare genetic diseases.

Factors associated with fetal karyotype in spontaneous abortion: a case-case study

BackgroundMost embryos that spontaneously abort during early pregnancy are found to have chromosomal abnormalities. The purpose of this study is to explore the factors involved in chromosome aberrations during embryogenesis.MethodsA case-case study was performed to compare the risk factors for spontaneous abortion with and without embryo chromosome aberration. A total of 160 cases of spontaneous abortion were enrolled from a tertiary general hospital in Kunming. KaryoLite BACs-on-Beads (KL-BoBs) and fluorescence in situ hybridization (FISH) were employed to determine chromosomal constitution of abortion chorion villus samples. Maternal serum levels of homocysteine (Hcy) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Information about clinical background and environmental exposure was collected through a self-designed questionnaire. To identify the inherited chromosomal abnormalities, couples with chromosomal abnormalities in abortus were recalled for karyotyping.ResultsThe overall rate of chromosomal abnormalities was 62.5% (100/160, KL-BoBs combined with FISH) including 51.9% (83/160) aneuploidies, 6.3% (10/160) polyploidies, and 4.4% (7/160) structural abnormalities. Only one case of structural abnormality was found to be inherited from maternal balanced translocation. Compared to abortus with normal karyotype, abortus with abnormal karyotype showed a positive association with parental age and elevated maternal serum homocysteine (Hcy) level, but negative association with previous miscarriage and perceived noise.ConclusionsEmbryonic chromosomal aberrations accounted for the majority of spontaneous abortion cases. A combination of internal and external factors may induce spontaneous abortion through fetal chromosomal aberrations or other pathogenic mechanisms.

Elevated serum homocysteine levels are associated with the development of chronic venous ulcers

Venous ulceration is a multifactorial disease, and whether hyperhomocysteinemia (HHcy) promotes deterioration from primary varicose veins to venous ulcers remains unproven. This study retrospectively analyzed clinical data from 717 patients to investigate the potential correlation between HHcy and primary varicose veins ulcer formation, including 611 patients without ulcers (control group) and 106 with ulcers (case group). In this study, 46.2% (49/106) of patients in the case group and 17.5% (107/611, p < 0.001) in the control group suffered from HHcy. Multivariate logistic analysis revealed that HHcy was closely associated with the incidence of venous ulceration in patients with primary varicose veins (p < 0.001). Propensity score matching created 101 matched pairs of patients with and without ulcers, and the analysis pointed to a potential link between HHcy and ulcer formation in the context of primary varicose veins (p < 0.001). Additional experiments showed that HHcy could induce endothelial dysfunction and phenotypic switching of vascular smooth muscle cells. Both clinical and experimental findings implicated HHcy as a key factor in the development of venous ulceration. Further research is needed to appraise the effectiveness of HHcy-lowering therapy in the prevention of venous ulcers in patients with varicose veins.

A cross-sectional study of comparison of elevated levels of serum Homocysteine in intracranial and extracranial atherosclerotic stenosis groups.

Introduction: The primary goal of this study was to compare serum homocysteine levels in acute ischemic strokes caused by extracranial atherosclerotic stenosis (ECAS) and intracranial atherosclerotic stenosis (ICAS)groups in order to see if there was a link between elevated serum homocysteine levels and ICAS. Methodology: The present study was a cross-sectional study done by the department of neurology at a tertiary level hospital in Mumbai. Various clinical, radiological &amp; laboratory parameters including serum Homocysteine were compared between patients with ECAS and ICAS stroke. Results: The study enrolled a total of 150 patients, with 110 in the ECAS group and 40 in the ICAS group. We observed that mean serum Homocysteine levels were 2.42 µg/ml in the ECAS group and 4.88 µg/ml in the ICAS group (p=0.01). High serum Homocysteine levels were more common in the ICAS group than in the ECAS group (55 percent versus 33.6 percent, p = 0.01). The lipid profile was found to be similar in the two study groups, except for low HDL, which was observed in 70 (64%) of the ECAS patients as compared to 17 (43%) of the ICAS (p-value &lt; 0.05). There was no statistical difference in the caparison of demographic and other risk factor profiles between ECAS and ICAS patients. Conclusions: High serum Homocysteine levels were found to be more common in the ICAS group than in the ECAS group.

Role of mutations in MTHFR gene and hyperhomocysteinemia in occurrence of ischemic stroke

The objective of the study is review and analyze scientific publications devoted to the problems of stroke, its relationship with the most common mutations in the MTHFR gene and their individual allelic variants and serum homocysteine levels.Materials and methods. Analyzing foreign and domestic publications, the relationship of the strongest mutations in the MTHFR gene with an increase in the level of serum homocysteine, which is a predictor of the development of vascular accidents, including acute circulatory disorders of the brain, was revealed.Results. Stroke is a socially significant disease. All risk factors for acute cerebral stroke are subdivided into modifiable and non-modifiable. To a non-modifiable factor that predisposes to the development of ischemic and hemorrhagic stroke, hereditary factors, including genetic mutations in a number of genes. MTHFR is a genome carrying individual allelic variants that can affect the level of homocysteine in blood serum, causing it to increase, and hyperhomocysteinemia, according to a number of studies, is a likely predictor of diseases of the cardiovascular system, including severe cerebrovascular accidents. At the same time, a large number of studies use the services of the protective role of reducing the elevated level of serum homocysteine using various forms of folic acid and B vitamins. The authors of the article attempted to process, analyze and summarize the data of modern research issues on the topic under consideration.Conclusions. The relationship between the occurrence of ischemic and hemorrhagic stroke and the most common mutations in the MTHFR gene has been revealed. Hyperhomocysteinemia, separate and developing as a result of these mutations, is an independent risk factor for the development of acute cerebral ischemia. Normalization of elevated serum homocysteine levels is required for all patients as stroke prevention, and includes not only the use of foods enriched with folic acid, but also pharmacological correction of folates and B vitamins.