Mukul Singal, Amir Mahmoud, Pradyumna Dinkar Phatak
{"title":"在专科诊所发现的 HFE C282Y/H63D 复合杂合子的临床特征：与 HFE C282Y 同合子的主要区别。","authors":"Mukul Singal, Amir Mahmoud, Pradyumna Dinkar Phatak","doi":"10.1080/17474086.2024.2337950","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Patients with p.C282Y homozygous (p.C282Y) <i>HFE</i> mutations are more likely to develop hemochromatosis (HC) than p.C282Y/p.H63D compound heterozygotes (p.C282Y/H63D).</p><p><strong>Research design and methods: </strong>We conducted a retrospective chart review of 90 p.C282Y and 31 p.C282Y/H63D patients at a referral practice to illustrate the differences in the natural history of the disease in these two HC cohorts.</p><p><strong>Results: </strong>Over a median follow-up of 17 years, p.C282Y had higher mean serum ferritin (1105 mg/dL vs. 534 mg/dL, <i>p</i> = 0.001) and transferrin saturations (75.3% vs. 49.5%, <i>p</i> = 0.001) at diagnosis. p.C282Y underwent more therapeutic phlebotomies (TP) till de-ironing (mean 24 vs. 10), had higher mean mobilized iron stores (4759 mg vs. 1932 mg), and required more annual maintenance TP (1.9/year vs. 1.1/year, <i>p</i> = 0.039). p.C282Y/H63D were more likely to have obesity (45.2% vs. 20.2%, <i>p</i> = 0.007) at diagnosis, with a non-significant trend toward consuming more alcohol. There was no significant difference in the development of HC-related complications between the two cohorts.</p><p><strong>Conclusions: </strong>p.C282Y have a higher mobilizable iron and require more TP. p.C282Y/H63D likely require additional insults such as obesity or alcohol use to develop elevated ferritin. De-ironing may mitigate the risk of developing HC-related complications.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"145-152"},"PeriodicalIF":2.3000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical characteristics of <i>HFE</i> C282Y/H63D compound heterozygotes identified in a specialty practice: key differences from <i>HFE</i> C282Y homozygotes.\",\"authors\":\"Mukul Singal, Amir Mahmoud, Pradyumna Dinkar Phatak\",\"doi\":\"10.1080/17474086.2024.2337950\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Patients with p.C282Y homozygous (p.C282Y) <i>HFE</i> mutations are more likely to develop hemochromatosis (HC) than p.C282Y/p.H63D compound heterozygotes (p.C282Y/H63D).</p><p><strong>Research design and methods: </strong>We conducted a retrospective chart review of 90 p.C282Y and 31 p.C282Y/H63D patients at a referral practice to illustrate the differences in the natural history of the disease in these two HC cohorts.</p><p><strong>Results: </strong>Over a median follow-up of 17 years, p.C282Y had higher mean serum ferritin (1105 mg/dL vs. 534 mg/dL, <i>p</i> = 0.001) and transferrin saturations (75.3% vs. 49.5%, <i>p</i> = 0.001) at diagnosis. p.C282Y underwent more therapeutic phlebotomies (TP) till de-ironing (mean 24 vs. 10), had higher mean mobilized iron stores (4759 mg vs. 1932 mg), and required more annual maintenance TP (1.9/year vs. 1.1/year, <i>p</i> = 0.039). p.C282Y/H63D were more likely to have obesity (45.2% vs. 20.2%, <i>p</i> = 0.007) at diagnosis, with a non-significant trend toward consuming more alcohol. There was no significant difference in the development of HC-related complications between the two cohorts.</p><p><strong>Conclusions: </strong>p.C282Y have a higher mobilizable iron and require more TP. p.C282Y/H63D likely require additional insults such as obesity or alcohol use to develop elevated ferritin. De-ironing may mitigate the risk of developing HC-related complications.</p>\",\"PeriodicalId\":12325,\"journal\":{\"name\":\"Expert Review of Hematology\",\"volume\":\" \",\"pages\":\"145-152\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17474086.2024.2337950\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/4/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17474086.2024.2337950","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：与p.C282Y/p.H63D复合杂合子（p.C282Y/H63D）相比，p.C282Y同源（p.C282Y）HFE突变患者更容易患血色沉着病（HC）：我们对一家转诊诊所的 90 名 p.C282Y 和 31 名 p.C282Y/H63D 患者进行了回顾性病历审查，以说明这两组 HC 患者的自然病史差异：结果：在中位 17 年的随访中，p.C282Y 患者确诊时的平均血清铁蛋白（1105 mg/dL vs. 534 mg/dL，p = 0.001）和转铁蛋白饱和度（75.3% vs. 49.5%，p = 0.001）较高。P.C282Y/H63D在确诊时更有可能肥胖（45.2% vs. 20.2%，p = 0.007），而且有更多饮酒的非显著趋势。p.C282Y/H63D可能需要肥胖或酗酒等额外刺激才能导致铁蛋白升高。除铁可降低患 HC 相关并发症的风险。
Clinical characteristics of HFE C282Y/H63D compound heterozygotes identified in a specialty practice: key differences from HFE C282Y homozygotes.
Background: Patients with p.C282Y homozygous (p.C282Y) HFE mutations are more likely to develop hemochromatosis (HC) than p.C282Y/p.H63D compound heterozygotes (p.C282Y/H63D).
Research design and methods: We conducted a retrospective chart review of 90 p.C282Y and 31 p.C282Y/H63D patients at a referral practice to illustrate the differences in the natural history of the disease in these two HC cohorts.
Results: Over a median follow-up of 17 years, p.C282Y had higher mean serum ferritin (1105 mg/dL vs. 534 mg/dL, p = 0.001) and transferrin saturations (75.3% vs. 49.5%, p = 0.001) at diagnosis. p.C282Y underwent more therapeutic phlebotomies (TP) till de-ironing (mean 24 vs. 10), had higher mean mobilized iron stores (4759 mg vs. 1932 mg), and required more annual maintenance TP (1.9/year vs. 1.1/year, p = 0.039). p.C282Y/H63D were more likely to have obesity (45.2% vs. 20.2%, p = 0.007) at diagnosis, with a non-significant trend toward consuming more alcohol. There was no significant difference in the development of HC-related complications between the two cohorts.
Conclusions: p.C282Y have a higher mobilizable iron and require more TP. p.C282Y/H63D likely require additional insults such as obesity or alcohol use to develop elevated ferritin. De-ironing may mitigate the risk of developing HC-related complications.
期刊介绍：
Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.
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