Klötzer Christina, Schnabel Franziska, Kubasch Anne-Sophie, Jentzsch Madlen, Franke Georg-Nikolaus, Uhlig Jens, Faust Helene, Jauss Robin-Tobias, Oppermann Henry, Popp Denny, Metzeler Klaus H, Lemke Johannes R, Vučinić Vladan, Platzbecker Uwe
University Leipzig Medical Center, Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig, Germany.
Comprehensive Cancer Center Central Germany, Leipzig, Germany.
Acta Haematol. 2025;148(4):380-385. doi: 10.1159/000542286. Epub 2024 Oct 28.
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 (MDS) 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 hemoglobin 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.
硫胺素反应性巨幼细胞贫血综合征（TRMA）是一种罕见的常染色体隐性疾病，由SLC19A2基因突变引起，该突变可以是纯合子或复合杂合子，其特征为巨幼细胞贫血、糖尿病（DM）以及儿童期起病的感音神经性听力损失。血清中的叶酸和维生素B12水平正常，骨髓中发育异常的红细胞生成常类似骨髓增生异常肿瘤（MDS），这是一种潜在的鉴别诊断。硫胺素替代治疗可使贫血恢复正常，但对听力损失或糖尿病无影响。
我们报告了一名38岁男性患者，自幼患有贫血、胰岛素依赖型糖尿病、视神经病变和白内障，病程长达12年。实验室检查显示为巨幼细胞贫血。其他指标正常。骨髓涂片显示红细胞生成异常伴巨幼细胞改变，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显示，母系等位基因的SLC19A2基因存在杂合错义变异，父系等位基因的1q24.2染色体区域存在3.4 Mb倒位，断点位于FAM78B和SLC19A2基因。开始每天口服100 mg硫胺素进行治疗，12周后血红蛋白水平和骨髓形态恢复正常。
对于具有指示性合并症和典型表型（可能类似MDS特征）的成年患者，应考虑迟发性TRMA。
