High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: Molecular and clinical findings of Turkish probands

Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta-synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype–phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829−2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n = 12, 46.2% neurological presentation), followed by thromboembolic events (n = 6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n = 5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%.     

Combined genetic mutations have remarkable effect on deep venous thrombosis and/or pulmonary embolism occurence

Purpose

Although deep vein thrombosis and thromboembolic diseases differ among various races, they are still important in our day. The difficulties in treatment and following-up of these diseases are caused by secret genetic mutations rather than predisposing factors.

Methods

Between January 2011 and May 2013, patients who were traced for deep vein thrombosis and/or pulmonary embolism were evaluated retrospectively. 84 patients (53.6% males and 46.4% females) were included in the study. Their family histories, predisposing factors and treatments were researched. Factor V Leiden (G 1691A), Factor II G20210A, Plasminogen Activator Inhibitor-Type 1 (4G/5G), and Methylene Tetrahydrofolate Reductase (C677T, A1298C) mutations were investigated from peripheral venous blood.

Results

Among the genetic mutations we searched, the incidence of single mutation rate was observed at 11.9%, double mutation collocation at 44%, triple mutation collocation at 29.8%, quadruple mutation collocation at 13.1%, and finally, quintuplet mutation collocation at 1.2%. Our approximate mutation number was found as 2.47 ± 0.91.

Conclusion

We observed that multiple mutations were high in number compared to single genetic mutations. The patients who have multiple mutations should be more in the front line considering their diagnosis, treatment and following up, and also in terms of decreasing mortality, morbidity and recurrence.     

子宫动脉栓塞术后并发血栓的临床病例分析和诊治探讨

目的:探讨剖宫产瘢痕妊娠(CSP)患者经子宫动脉栓塞术(UAE)后并发下肢深静脉血栓(DVT)的临床病例的诊断治疗要点。方法:回顾性分析2014年-2016年我院收治的剖宫产瘢痕妊娠患者经子宫动脉栓塞术后并发下肢深静脉血栓(DVT)5例患者的临床特点及诊断、治疗方法。结果:2014年-2016年,我院CSP患者经UAE治疗后发生DVT的发病率为1.63%,患者平均年龄35.2岁。DVT临床症状出现于UAE术后3-6天,多表现为下肢的疼痛及酸胀,深静脉血栓均出现在介入穿刺处肢体。用彩色多普勒血流显像诊断深静脉血栓安全可靠。采用低分子肝素皮下注射抗凝治疗均取得较好效果。结论:剖宫产瘢痕妊娠患者经子宫动脉栓塞术治疗后有发生下肢深静脉血栓风险,DVT发生与穿刺处肢体制动,血管受压,血液回流障碍有关。手术前后应采取预防措施,低分子肝素钠抗凝对DVT治疗有效。     

Label-free high frame rate imaging of circulating blood clots using a dual modal ultrasound and photoacoustic system

Deep vein thrombosis (DVT) is a disorder when a blood clot (thrombus) is formed in one of the deep veins. These clots detach from the original sites and circulate in the blood stream at high velocities. Diagnosing these blood clots at an early stage is necessary to decide the treatment strategy. For label-free, in vivo, and real-time detection, high framerate photoacoustic imaging can be used. In this work, a dual modal clinical ultrasound and photoacoustic (PA) system is used for the high framerate PA imaging of circulating blood clots in blood at linear velocities up to 107 cm/sec. Blood clot had 1.4 times higher signal-to-noise ratio (SNR) in the static mode and 1.3 times higher SNR compared to blood PA signal in the flow experiments. This work demonstrates that fast-moving circulating blood clots are easy to recognize against the background PA signal and may aid in early diagnosis.     

Influence of lipid metabolism disorders on venous thrombosis risk

Background: To investigate the influence of lipid metabolism disorders on the risk of deep vein thrombosis. Methods: A total of 200 subjects participated in the study, 100 of whom experienced DVT with or without PTE, and 100 healthy subjects representing the control group. We classified patients and controls in terms of serum concentrations of chylomicrons, LDL, IDL, VLDL, and HDL particles, as those with or without hyperlipoproteinemia and in terms of serum Lp (a) lipoprotein levels, as those with hyperLp (a) lipoproteinemia (serum Lp (a) values >0.3 g/L) and those without hyperLp (a) lipoproteinemia (serum Lp (a) values <0.3 g/L). Based on the modified and supplemented Fredrickson classification, participants with verified existences of hyperlipoproteinemia were classified into subgroups based on the type of hyperlipoproteinemia. Unconditional logistic regression was used to calculate ORs with 95% CIS as a measure of the relative risks for venous thrombosis in participants with hyperlipoproteinemia compared with those without hyperlipoproteinemia. The analysis was adjusted for all potential confounders (age, sex, obesity) related to the functionality of the lipid metabolism, and at the same time, may have an impact on the risk of venous thrombosis. Results: The results of the comparison of the mean values of individual lipid status parameters between the patient group and the control group clearly indicate higher concentrations of total cholesterol (5.93 mmol/L vs. 5.52 mmol/L), total triglycerides (1.58 mmol/L vs. 1.50 mmol/L), and LDL-cholesterol (3.83 mmol/L vs. 3.44 mmol/L) in the patient group relative to the control group, with a statistically significant difference observed only in the case of LDL-cholesterol concentrations. We have found that type IIa hyperlipoproteinemia is associated with a nearly double increased risk for deep vein thrombosis (OR 1.99; Cl 1.01-3.90), while type IIb, IV, or hyperLp (a) lipoproteinemia did not influence the risk (OR 1.22; 95% Cl 0.79-1.84; OR 0.89; 95% Cl 0.52-1.54 OR 1.85; 95% CI 0.84-4.04). Conclusions: Hypercholesterolemia doubles the risk of deep vein thrombosis development.