ĐẶC ĐIỂM LÂM SÀNG CỦA THAI PHỤ SẨY THAI LIÊN TIẾP KHÔNG RÕ NGUYÊN NHÂN MANG GEN METHYLENETETRAHYDROFOLATE REDUCTASE BỆNH LÝ

Nguyên nhân sẩy thai liên tiếp rất phức tạp và khó xác định, trong đó đa hình đơn gen MTHFR bệnh lý (C677T, A1298C) là một nguyên nhân mới cần tìm hiểu. Nghiên cứu nhằm: Xác định mối liên quan giữa MTHFR và bệnh lý sảy thai liên tiếp; Mô tả đặc điểm lâm sàng của những thai phụ có tiền sử sảy thai liên tiếp mang gen MTHFR (C677T và A1298C) bệnh lý. Đây là 1 nghiên cứu bệnh- chứng, 2 nhóm đều được xác định kiểu gen của gen MTHFR C677T/A1298C bằng phương pháp PCR. Nghiên cứu thu được 43 thai phụ thuộc nhóm bệnh và 30 thai phụ thuộc nhóm chứng. Thời điểm thai sẩy trung bình trong tiền sử của nhóm mang kiểu gen bệnh lý là 8,47 tuần. MTHFR C677T làm tăng nguy cơ xuất hiện triệu chứng doạ sẩy thai trong 3 tháng đầu (p=0,043). Kết luận: Đa hình đơn gen MTHFR C677T tăng xuất hiện triệu chứng doạ sẩy thai trong 3 tháng đầu.

BƯỚC ĐẦU ĐÁNH GIÁ KẾT QUẢ ĐIỀU TRỊ FOLAT Ở BỆNH NHÂN SẨY THAI LIÊN TIẾP MANG GEN MTHFR ĐỘT BIẾN

Sảy thai liên tiếp và đột biến gen MTHFR được ghi nhận có liên quan rõ rệt ở chủng tộc da vàng. Điều trị folat có thể làm giảm nồng độ homocystein trong máu cải thiện kết cục thai kỳ. Mục tiêu: của nghiên cứu đánh giá kết quả điều trị bằng folate đối với bệnh nhân mang gen đột biến MTHFR C677T tại bệnh viện Phụ Sản Hà Nội. Nghiên cứu mô tả cắt ngang trên 30 bệnh nhân có tiền sử sẩy thai liên tiếp mang gen đột biến MTHFR được điều trị 5 mg Folat/ ngày trong 3 tháng. Kết quả 100% bệnh nhân mang gen MTHFR dạng dị hợp tử CT. Nồng độ trung bình của homocystein trước và sau điều trị lần lượt là 10,3±3,47; 6,8±2,48µmol/l, ( p=0,000). Kết luận: điều trị folat trong 3 tháng liên tục làm giảm nồng độ homocystein trong máu.

Individualized Folic Acid Supplementation based on Polymorphisms of Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase Reductase (MTRR), Compared with Traditional Folic Acid Supplementation, Reduces Gestational Diabetes Mellitus

Backgroud: Folic Acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but existing studies are inconsistent. We examined the genotype distributions and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms of pregnant women in China, and compared the effects of individualized folate supplementation and traditional FA supplementation on GDM.Methods: The genotype distributions and allele frequencies of MTHFR C677T, A1298C and MTRR A66G polymorphisms in 968 pregnant women (case group) were tested. FA metabolism was ranked at four levels, and then pregnant women of different levels are supplemented with different doses of FA at different periods. The case group was followed up for pregnancy complications and compared with 1,940 pregnant women traditionally supplemented with FA in the same hospital (control group).Results: The allele frequencies of MTHFR C677T were 63.3% (C) and 36.7% (T), those of MTHFR A1298C were 79.3% (A) and 20.7% (C), and those of MTRR A66G were 75.0% (A) and 25.0% (G). Compared with control group, the incidence of GDM in the case group were significantly lower, especially in high-risk pregnant women after FA supplementation.Conclusion: Traditional FA supplementation based on personal habits is controversial, but the use of polymorphisms of genes to clarify the FA metabolism of pregnant women, appropriate, timely and accurate supplementation of FA can effectively reduce gestational diabetes, especially for high-risk pregnant women.

Relationship between Methylenetetrahydrofolate Reductase C677T Homozygous Mutation and Cerebral Small Vessel Disease Subtypes

Background: Neuroimaging detects cerebral small vessel disease (CSVD) subtypes, including infarction, asymptomatic lacunes, cerebral microbleeds, white matter hyperintensities (WMHs), and enlarged perivascular space. Methylenetetrahydrofolate reductase (MTHFR) plays an essential role in the metabolism of folic acid and homocysteine. The purpose of this study was to investigate the relationship between the MTHFR C677T mutation and CSVD subtypes.Methods: A total of 144 patients with acute ischemic stroke who visited the Korea University Guro Hospital between April 2020 and August 2020 were retrospectively reviewed. After excluding 24 patients, due to missing laboratory, clinical, or imaging information, a total of 120 patients were analyzed.Results: Among the 120 participants, 25% were included in the MTHFR C677T homozygous mutation group, which had significantly lower folic acid levels (6.24±4.21 ng/mL vs. 8.24±4.21 ng/mL, p=0.03) and higher total homocysteine levels (17.09±14.07 μmol/L vs. 9.65±3.19 μmol/L, p<0.01). Using multiple logistic regression analysis, the homozygous mutation (adjusted odds ratio [aOR]=4.29; 95% confidence interval [CI]=1.16–15.90) and age (aOR=1.06; 95% CI=1.01–1.11) were independently associated with moderate to severe WMHs. Additionally, moderate to severe WMHs were more frequent in the homozygous mutation group (86.7% vs. 66.7%, p=0.01). In a detailed analysis, the homozygous mutation group showed a significantly higher rate of moderate to severe periventricular WMH (PWMH) (86.7% vs. 65.6%, p<0.01).Conclusion: The MTHFR C677T homozygous mutation was positively correlated with moderate to severe PWMH subtypes of CSVD.

Sudden Onset of Vestibular Migraine Complicated with BPPV and Mal de Debarquement Syndrome – a Diagnostic Dilemma

Vestibular migraine is combination of migraine and vestibular symptoms. In clinical examination it can be replaced with benign paroxysmal positional vertigo (BPPV) cupulolithiasis, but also BPPV is common comorbidity in migraine patients. There is also high association between vestibular migraine and Mal de Debarquement syndrome. Patient came to hospital with vertigo that was diagnosed as left PC-BPPV canalolithiasis. After first Epley's maneuver symptoms didn't resolved. Week after, at second Epley's maneuver performed patient developed left PC-BPPV cupulolithiasis. Month after, at third Epley's maneuver BPPV resolved but patient developed Mal de Debarquement syndrome. Laboratory testing showed hyperhomocisteinemia and homozygous MTHFR C677T and PAI, with low vitamin D. After reviewing the vestibular symptoms in the first attack which was misdiagnosed as BPPV canalolithiasis, and history of migraine, patient was diagnosed with vestibular migraine. Patient well responded to migraine diet and supplementation with B complex. Vestibular disorders are similar to each other and they can overlap. More attention in taking detailed medical history should be given to patients with vertigo or dizziness.

ĐÁNH GIÁ LIÊN QUAN GIỮA CÁC ĐA HÌNH GEN GÂY RỐI LOẠN CHUYỂN HÓA HOMOCYSTEINE VỚI SẢY THAI LIÊN TIẾP

Mục tiêu: đánh giá mối liên quan giữa các đa hình gen MTHFR C677T, MTHFR A1298C, MTR A2756G và MTRR A66G gây rối loạn chuyển hóa homocysteine với sảy thai liên tiếp không rõ nguyên nhân ở phụ nữ Việt Nam. Đối tượng và phương pháp nghiên cứu: nghiên cứu bệnh – chứng, đa trung tâm tiến hành trên 92 phụ nữ sảy thai liên tiếp không rõ nguyên nhân và 92 phụ nữ khỏe mạnh. Kết quả: tuổi trung bình của nhóm bệnh và nhóm chứng lần lượt là 29,58 ± 2,91 và 30,69 ± 2,44. Allele đột biến của đa hình MTHFR C677T và MTR A2756G gặp nhiều hơn có ý nghĩa thống kê ở những bệnh nhân sảy thai liên tiếp (p > 0,05), các đột biến này làm tăng nguy cơ sảy thai liên tiếp lần lượt là 2,33 và 1,82 lần so với nhóm chứng (OR 2,33; 95% CI, 1,38-3,96 và OR 1,82; 95% CI, 1,02-3,29). Mặt khác, đột biến thay thế nucleotid A thành C ở gen MTHFR A1298C và thay thế nucleotid A thành G ở gen MTRR A66G không không làm tăng nguy gây bệnh trong nghiên cứu của chúng tôi (P > 0,05). Kết luận: đa hình MTHFR C677T và MTR A2756G là yếu tố nguy cơ của sảy thai liên tiếp ở phụ nữ Việt Nam, kết quả này tương đồng với nhiều nghiên cứu trên thế giới. Trên cơ sở đó chúng tôi kiến nghị tiến hành xét nghiệm phát hiện đa hình gen liên quan chuyển hóa homocysteine ở những người phụ nữ xảy thai liên tiếp chưa rõ nguyên nhân.

A Case of Budd-Chiari Syndrome Associated with Erythrocytosis and Homozygous MTHFR C677T Mutation

An erythrocytosis describes an increased erythrocyte, subclassified into relative due to hemoconcentration or absolute by an increase in erythrocyte mass, defined as an increase in hemoglobin concentration and/or hematocrit in the peripheral blood above the sex-specific normal range. Budd-Chiari Syndrome (BCS) is related to an obstruction of the hepatic venous flow leading to occlusion of hepatic veins and their tributaries. Genetic and environmental factors can interact for risk determination of venous thromboembolism. The risk associated with SNP 677C>T and 1298A>C of the methylenetetrahydrofolate reductase (MTHFR), 1691G>A of the Factor V Leiden (FVL) and 20210G>A of the prothrombin (FII) genes were investigated in many studies involving thrombosis. This case report describes the clinical, hematological and biochemistry data about a 48-year-old woman diagnosed with PV and a BCS associated, also carrying 677C>T SNP in homozygosity. The patient started therapy with phlebotomy, hydroxyurea and oral anticoagulant. Currently, she presents a better clinical and laboratory condition with normalized values of hematological and platelet indices. This case report aims to contribute with evidence of related comorbidities and makes it possible to report that genetic factors are involved since the patient's mother had already been diagnosed with absolute erythrocytosis in 2016 at 78 years old. For this main result, we understand that it is clear that a family genetic study can reveal clinical modifying factors in these patients, as there are different clinical severities in the family. Furthermore, we believe in the need for a greater number of randomized clinical trials to add better evidence to complement an ideal therapeutic approach in these patients.

Transmission Jeopardy of Adenomatosis Polyposis Coli and Methylenetetrahydrofolate Reductase in Colorectal Cancer

Colorectal cancer (CRC) is one of the globally prevalent and virulent types of cancer with a distinct alteration in chromosomes. Often, any alterations in the adenomatosis polyposis coli (APC), a tumor suppressor gene, and methylenetetrahydrofolate reductase (MTHFR) gene are related to surmise colorectal cancer significantly. In this study, we have investigated chromosomal and gene variants to discern a new-fangled gene and its expression in the southern populations of India by primarily spotting the screened APC and MTHFR variants in CRC patients. An equal number of CRC patients and healthy control subjects ( n = 65 ) were evaluated to observe a chromosomal alteration in the concerted and singular manner for APC and MTHFR genotypes using standard protocols. The increasing prognosis was observed in persons with higher alcoholism and smoking ( P < 0.05 ) with frequent alterations in chromosomes 1, 5, 12, 13, 15, 17, 18, 21, and 22. The APC Asp 1822Val and MTHFR C677T genotypes provided significant results, while the variant alleles of this polymorphism were linked with an elevated risk of CRC. Chromosomal alterations can be the major cause in inducing carcinogenic outcomes in CRCs and can drive to extreme pathological states.

New Insight of Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphisms, and Serum Electrolytes in Cardiac Syndrome X Patients

Background: Cardiac Syndrome X (CSX) is a condition affecting the cardiovascular system with a significant degree of morbidity. Diagnosis and treatment are challenging when the cause is unclear. Subsequently, a molecular marker for screening of people with CSX is highly recommended. The present study evaluated the association between MTHFR C677T gene polymorphism among Sudanese patients with CSX. Materials and Methods: A total of 100 subjects were enrolled. Venous blood sample was collected from each participant in Ethylene Diamine Tetracetic Acid (EDTA) containers. DNA was extracted from blood samples using guanidine chloride method and MTHFR mutation was detected by PCR-restriction fragment polymorphism (PCR-RFLP). Statistical package for social sciences (SPSS) was used to analyze data. Results: Most patients 30(60%) were females, their age ranged between 30-60 with mean age 44.98±7.34 SD. MTHFR 677CT genotype frequency was statistically significant (P≤0.014), where 10(20%) had 677CT and 1(2%) had 677TT among patients group respectively compared to control individuals who had only 2(4%) 677CT. T alleles were significantly more frequent among our participant than C alleles. There is insignificant slightly decreased (2.4 ±2.8, and 2.5±3.2) in serum magnesium levels among patients compared to control respectively, as well as random blood glucose. Elevated mean levels of total cholesterol, and HDL among patients (182 ±18.1, and 49.7±7.1) vs (180 ±20.3, and 46.6 ±11.3) among control group, all findings were statistically non-significant. Slightly decrease in magnesium level (2.2 ±2.1, vs 2.9 ±0.8) among heterozygous CT genotypes compared to homozygous genotypes. Conclusion: MTHFR C677T is linked to CSX in the Sudanese population, and serum magnesium level was slightly decreased among heterozygous MTHFR C677T. Furthermore, the mutation could be used as a disease molecular screening technique.

Use of the extracorporeal detoxification methods for methotrexate elimination

The article considers a clinical case of a 12-year-old child with osteosarcoma of the left tibia, T1N0M0G3, treated with high-dose methotrexate 12 g/m2. As a result of delayed elimination of methotrexate, the patient developed acute liver failure. The ALT level increased to 4790 U/L, AST — to 4320 U/L, which indicates life-threatening acute liver damage. There was no coagulopathy, significant increase in bilirubin, and hepatic encephalopathy. The timely use of efferent therapy allowed avoiding the complete course of acute liver failure. The patient received intravenous hydration therapy and urine alkalinization with 3000 ml/m2/day of 5% glucose in combination with 20 μmol NaHCO3/L and 20 μmol KCl/L. The urine output was more than 600 ml/m2/6 hours. Additionally, antidote therapy with calcium folinate was administered. In this case, we used continuous venous-venous hemodiafiltration using Prismaflex. After the first session, which lasted for 78 hours, there was a re-increase in serum methotrexate concentration and ALT, AST levels, which indicates a large volume of distribution of methotrexate and the need for long-term extracorporeal therapy. Therefore, the second session of continuous venous-venous hemodiafiltration was provided. After the second session, there was no re-increase in methotrexate level in the blood and the transaminases and total bilirubin returned to normal levels. Additionally, the patient was tested for homocysteine levels for hyperhomocysteinemia, as well as 4 genes that also determine the predisposition to hyperhomocysteinemia — methylenetetrahydrofolate reductase gene MTHFR C677T, A1298C, methionine synthase MTRR, and MTR. The presence of elevated levels of homocysteine, as well as heterozygosity of these genes, indicate a slow excretion of methotrexate or a complete delay in its excretion. Our patient presented the negative results of these tests. Conclusions. This clinical case indicates the effectiveness of continuous venous-venous hemodiafiltration in combination with intravenous hydration, urine alkalinization, and antidote therapy in the treatment of hepatotoxicity of high-dose methotrexate on the background of delayed excretion.