A Novel Compound Heterozygous Mutation in a Chinese Boy with Thiamine-responsive Megaloblastic Anemia - EAP 2017 Congress and MasterCourse, October 12-15, 2017, Ljubljana, Slovenia

Guoying Chang ¹ Xin Li ¹ Qun Li ¹ Yu Ding ¹ Juan Li ¹ Yao Chen ¹ Guoying Chang ¹ Jian Wang ² Xiumin Wang ¹ Yijin Gao ³

¹Department of Endocrinology and Metabolism, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine
²Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine
³Department of Haematology and Haematological Oncology, Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine

Background: Thiamine-responsive megaloblastic anemia (TRMA), a rare autosomal recessive inherited disease, is characterized by the clinical traid of diabetes mellitus, megalobastic anemia, and sensorineural deafness. Some of these symptoms can be relieved by therapeutic dose of thiamine. To date, only 100 cases have been reported in the world and 4 in China. We aim to report a novel compound heterozygous mutation in a 6 years old Chinese boy who presented with typical clinical features of TRMA.

Methods: We collected the boy’s clinical presents, and past history. Then we did some examinations for him, such as CBC, serum glucose, serum insulin, serum iron and so on; Besides, the boy was evaluated by the targeted next generation sequencing using his peripheral blood genomic DNA, and the relevant mutation was verified with Sanger sequencing.

Results: The boy presented diabetes mellitus, anemia and deafness. Meanwhile, he also presented thrombocytopenia, leukopenia, horizontal nystagmus, thrombocytopenia, leukopenia, ventricular premature beat, hepatomegaly, and short stature. DNA sequencing revealed a novel compound heterozygous mutation in SLC19A2: (1) gene duplication c.405dupA, p.Ala136Serfs*3 (heterozygous); (2) nucleotide deletion c.903delG p.Trp301Cysfs*13 (heterozygous). The boy was diagnosed with typical TRMA. After thiamine therapy, the diabetes and anemia of him was improved.

Conclusions: This is the first report of SLC19A2 gene heterozygous mutation in Chinese patient, our finding expands the mutant spectrum of SLC19A2 gene and adds new understanding of the phenotype.

Key words: Thiamine-responsive megaloblastic anemia; SLC19A2 gene; novel mutation; diabetes; megaloblastic; deafness; targeted next generation sequencing