Elstein D, Renbaum P, Levy-Lahad E, Zimran A
Gaucher Clinic, Shaare Zedek Medical Center, Jerusalem, Israel.
Am J Med Genet. 2000 Dec 18;95(5):429-31. doi: 10.1002/1096-8628(20001218)95:5<429::aid-ajmg4>3.0.co;2-6.
An inherited risk for thrombosis, including mutant thermolabile variant of methylenetetrahydrofolate reductase (MTHFR), factor V Leiden, or prothrombin may be the co-factor(s) for avascular necrosis (AVN) in patients with sickle cell disease. Similarly, heterozygosity for factor V Leiden is sufficient to explain the increased blood viscosity observed in children with Legg-Calve-Perthes disease who develop AVN. Because there are no laboratory tests or clinical markers that are helpful in predicting which patients with Gaucher disease may develop AVN, the current study was undertaken to ascertain if there exists an inherited predilection to hypercoagulability in patients with Gaucher disease and AVN. Analysis was performed on genomic DNA extracted from 56 adult patients with type I Gaucher disease. In this cohort of Ashkenazi Jewish patients, the frequency of mutations in the MTHFR, prothrombin, and factor V Leiden genes was found to be low, as was the presence of anticardiolipin antibodies; and none was correlated with increased incidence of AVN. Splenectomy, that may be a predisposing factor to AVN in patients with Gaucher disease, was factored out. Hence the presence of any of the above thrombophilic factors, and which by extension may be risk factors for AVN in other diseases, are not more common in patients with Gaucher disease who develop AVN. Studies in larger cohorts and possibly inclusion of additional factors may be needed to ascertain whether a correlation exists.
血栓形成的遗传风险，包括亚甲基四氢叶酸还原酶（MTHFR）的突变热不稳定变体、凝血因子V莱顿突变或凝血酶原突变，可能是镰状细胞病患者发生无血管性坏死（AVN）的辅助因素。同样，凝血因子V莱顿杂合性足以解释患有AVN的Legg-Calvé-Perthes病儿童中观察到的血液粘度增加。由于没有实验室检查或临床标志物有助于预测哪些戈谢病患者可能发生AVN，因此进行了本研究，以确定戈谢病合并AVN患者是否存在遗传性高凝倾向。对从56例成年I型戈谢病患者提取的基因组DNA进行了分析。在这组阿什肯纳兹犹太患者中，发现MTHFR、凝血酶原和凝血因子V莱顿基因的突变频率较低，抗心磷脂抗体的存在情况也是如此；且均与AVN发病率增加无关。脾切除术可能是戈谢病患者发生AVN的一个易感因素，已被排除。因此，上述任何一种血栓形成倾向因素，以及由此可能成为其他疾病中AVN危险因素的因素，在发生AVN的戈谢病患者中并不更常见。可能需要对更大的队列进行研究，并可能纳入其他因素，以确定是否存在相关性。
