Case Report: Genetic and Clinical Features of Maternal Uniparental Isodisomy-Induced Thiamine-Responsive Megaloblastic Anemia Syndrome

Background: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive hereditary disease due to mutations in SLC19A2. Some cases show familial inheritance. Case report: A female patient (from a gravida 1, para 1 mother) of 3.5 years of age was admitted to the Pediatric Hematology Department of Xianyang Caihong Hospital in June 2019. The patient had severe anemia, acupoint-size bleeding spots, and a few ecchymoses all over her body, as well as astigmatism and hyperopia. Hearing was normal. The patient had diabetes. Bone marrow biopsy suggested a myelodysplastic syndrome. The patient had a c.515G>A (p.G172D) homozygous mutation of SLC19A2 (NM_006996), indicating TRMA. Genetic testing revealed that the two alleles were inherited from her mother alone due to maternal uniparental isodisomy (UPD). The patient was treated with thiamine and a subcutaneous injection of insulin. The patient recovered well and was discharged. She continued thiamine and insulin at the same dose and was followed once a month. The last follow-up on September 15, 2020, showed no anemia or bleeding. She had a sound hearing and normal blood routine and fasting glucose levels. Hyperopia and astigmatism did not improve. Conclusion: The patient had TRMA induced by the c.515G>A (p.G172D) homozygous mutation of SLC19A2 inherited through maternal UPD. The genetic diagnosis of TRMA is of significance for guiding clinical treatment. Early treatment with exogenous thiamine can improve some of the clinical features of TRMA.