ESPE Abstracts

Background: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by a triad of megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus (DM). It is due to an inherited mutation in SLC19A2 gene, encoding a high-affinity thiamine transporter 1 in charge of facilitating the uptake of thiamine by the cells. Other manifestations including optic atrophy and stroke are rarely reported. We herein report an extremely rare case of TRMA without megaloblastic anemia, with associated stroke, and optic atrophy.

Case history: A 1-year-old girl born to consanguineous parents presented with right focal convulsions, hemiplegia, and photophobia. She was diagnosed with left-sided stroke and epilepsy. Her thrombophilia profile was normal, apart from heterozygous MTHFR gene mutation with normal homocysteine level. Within the period of her admission, hyperglycemia was incidentally discovered and she was diagnosed with DM, with low C-peptide (0.1 ng/ml), and HbA1C 7%. Her fundus examination revealed bilateral optic atrophy. After discharge, she started having difficulty hearing. Audiometry was done showing profound sensorineural hearing loss at high frequencies. At the age of 3 years, she presented with fever, pallor, and purpuric spots all over her body. She had been receiving iron therapy for 3 months, but with no improvement. On examination, she had mild hepatosplenomegaly. Her blood count showed normocytic normochromic anemia (MCV 81 fl) with reticulocytic count 3.6%, thrombocytopenia (plt 15.000/µl), neutropenia (ANC 700/µl), and activated lymphocytes. Cytomegalovirus-induced pancytopenia was suspected to be the cause of her hematological findings with positive CMV IgM, IgG. Other investigations including urine analysis, ANA, anti-dsDNA, C3, D-dimer, fibrinogen were normal, and Coomb’s test was negative. Pancreatic autoantibodies were done to confirm non-type 1 DM and were negative. Despite that she didn’t have macrocytic anemia, bone marrow with Prussian blue stain revealed sideroblastic anemia with ringed sideroblasts confirming the diagnosis of TRMA. On thiamine therapy (50 mg/day), her hematological findings, and her HbA1c normalized (5.6%) on insulin requirement 0.5 U/Kg/day. Later on, her genetic testing confirmed the diagnosis with homozygous mutation for a pathogenic non-sense variant of SLC19A2 gene.

Conclusions: TRMA syndrome should be kept in mind in the differential diagnosis of DM with deafness. It does not always have to be a classical presentation with all the cardinal features, so a high index of suspicion is needed. BM with Prussian blue stain demonstrating ringed sideroblasts is helpful in diagnosis-even if no megaloblastic anemia is present.