Thiamine-Responsive Megaloblastic Anemia (TRMA) Syndrome mimicking myelodysplastic neoplasm (MDS).

IF 1.7 4区 医学 Q3 HEMATOLOGY
Christina Klötzer, Franziska Schnabel, Anne-Sophie Kubasch, Madlen Jentzsch, Georg-Nikolaus Franke, Jens Uhlig, Helene Faust, Robin-Tobias Jauss, Henry Oppermann, Denny Popp, Klaus H Metzeler, Johannes R Lemke, Vladan Vučinić, Uwe Platzbecker
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Abstract

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing-loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDN) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing-loss or DM. We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later Hb levels and bone marrow morphology had normalized. Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS.

模仿骨髓增生异常肿瘤(MDS)的硫胺素反应性巨幼红细胞贫血(TRMA)综合征。
硫胺素反应性巨幼细胞性贫血综合征(TRMA)是一种罕见的常染色体隐性遗传病,SLC19A2 基因发生同源或复合杂合子突变,表现为巨幼细胞性贫血、糖尿病(DM)和感音神经性听力损失,儿童期发病。血清中的叶酸和维生素 B12 正常,骨髓中的红细胞生成障碍常与骨髓增生异常性肿瘤(MDN)相似,这是一个潜在的鉴别诊断。硫胺素替代可使贫血恢复正常,但对听力损失或 DM 没有影响。我们报告了一名 38 岁男性患者的情况,他自幼患有贫血、胰岛素依赖性糖尿病、视神经病变和白内障,病史长达 12 年。化验结果显示他患有巨幼红细胞性贫血。其他数值正常。骨髓涂片显示红细胞生成障碍并伴有巨幼红细胞病变,细胞遗传学和分子遗传学检查结果正常。基于下一代测序的诊断结果显示,母系等位基因中的 SLC19A2 基因存在杂合错义变异,父系等位基因中的 1q24.2 染色体区域存在 3.4 Mb 反转,其中 FAM78B 和 SLC19A2 存在断裂点。患者开始每天口服 100 毫克硫胺素,12 周后血红蛋白水平和骨髓形态恢复正常。晚发型TRMA应考虑用于具有指示性合并症和典型表型的成年患者,其表型可能会模仿MDS的特征。
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来源期刊
Acta Haematologica
Acta Haematologica 医学-血液学
CiteScore
4.90
自引率
0.00%
发文量
61
审稿时长
6-12 weeks
期刊介绍: ''Acta Haematologica'' is a well-established and internationally recognized clinically-oriented journal featuring balanced, wide-ranging coverage of current hematology research. A wealth of information on such problems as anemia, leukemia, lymphoma, multiple myeloma, hereditary disorders, blood coagulation, growth factors, hematopoiesis and differentiation is contained in first-rate basic and clinical papers some of which are accompanied by editorial comments by eminent experts. These are supplemented by short state-of-the-art communications, reviews and correspondence as well as occasional special issues devoted to ‘hot topics’ in hematology. These will keep the practicing hematologist well informed of the new developments in the field.
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