Case Presentation: A 19-year-old male with type 1 diabetes mellitus, congenital retinal dystrophy, and a family history of sensorineural hearing loss (SNL) presented with 2 weeks of fatigue and dyspnea. On arrival, the patient was tachycardic at 115 beats per minute and physical exam was notable for pallor. He was found to have a white blood cell count of 3.01 x 10^3/mm3, a red blood cell count of 5.7 x 10^6/mm3, and a platelet count of 24 x 10^3/mm3. Thiamine, vitamin B6, B9, B12, copper, and zinc levels were within normal limits. Human immune deficiency virus and hepatitis serologies were negative. Flow cytometry studies for leukemia, lymphoma and paroxysmal nocturnal hemoglobinuria were negative. Peripheral smear showed 41% lymphocytes with metamyelocytes, myelocytes, immature granulocytes blood, tear drop cells, and nucleated red blood cells. There were no blasts appreciated on peripheral smear. Bone marrow biopsy of the right posterior superior iliac spine demonstrated hypercellular marrow showing erythropoiesis with ring sideroblasts and dysmegakaryopoiesis. The diagnosis was unclear based on findings but was consistent with bone marrow failure. The patient was treated with supportive measures including supplemental oxygen and blood transfusions with resolution of symptoms and normalization of his complete blood cell count His plan for outpatient management was to follow up with weekly labs and blood transfusions occurring three times per week.One month later the patient had a recurrence of pancytopenia in the setting of normal cytogenetic studies and next-generation sequencing. Studies from his initial bone marrow biopsy later returned with two abnormal variants of the SLC19A2 gene. Due to his personal history of type 1 diabetes mellitus, congenital retinal dystrophy, and a family history of SHL in the setting of SLC19A2 variants, he was suspected to have thiamine-responsive megaloblastic anemia (TRMA). He was treated with oral thiamine and after several weeks of treatment, he had a complete resolution of pancytopenia.
Discussion: When investigating pancytopenia, it’s important for an internist to recognize potential genetic causes. TRMA is a genetic hematologic disorder that comprises the triad of sideroblasts, diabetes mellitus, and progressive SNL. (1) The SLC19A2 gene codes for a membrane protein functioning as a transporter of thiamine across the cell membrane. Variants in this gene make individuals particularly sensitive to thiamine depletion. (2)It has been found that supplementation of thiamine can reduce insulin requirement and anemia in these individuals. The SNL unfortunately has been shown to be irreversible. (3) Treatment requires lifelong oral thiamine (50-100 mg/day) along with transfusions for severe bouts of anemia. Patients should be screened and followed for SNL, diabetes mellitus, ophthalmologic, cardiovascular, and neurologic manifestations. The disease is inherited in an autosomal recessive manner, with recommendation that at-risk family members be tested. (4)
Conclusions: TRMA is a rare hematologic disorder that presents as megaloblastic anemia with a triad of sideroblastic anemia, SNHL, and diabetes mellitus in younger patient populations. It is important to identify the disease early via SLC19A2 gene analysis given thiamine supplementation can decrease insulin requirements and reverse anemia in these individuals.