P-234: Infantile diabetes and cytopenias unmasking thiamine-responsive megaloblastic anemia syndrome
M Abid, M Ibrahim, M Gul, V Rai, m. riazAbstract
Introduction
Thiamine-responsive megaloblastic anemia syndrome is a rare, autosomal recessive disease that is initiated by along with pathogenic variants in SLC19A2. It is classically characterized by diabetes mellitus, megaloblastic anemia, and sensorineural hearing loss, but the presentation can be incomplete during childhood.
Objectives
To describe the diagnostic journey and early therapeutic response in an infant with diabetes and persistent cytopenias diagnosed with thiamine-responsive megaloblastic anemia syndrome.
Methods
This is a case study that reports a 9-month-old male with diabetes diagnosed at 8 months after fever, polyuria, weight loss, and hyperglycemia. He had recurrent admissions for fever, cough, cytopenias, and anemia requiring transfusion. Clinical evaluation, serial blood counts, nutritional workup, bone marrow examination, and targeted exome sequencing were performed.
Results
The infant was born to consanguineous parents, and the important family history was a sibling’s death at the age of 9 months old. Investigations revealed that there was chronic bicytopenia with macrocytosis even after normal serum B12, folate, and iron tests with normal hemoglobin electrophoresis. Bone marrow biopsy showed hypercellular marrow and preserved trilineage hematopoiesis, mild dyshematopoiesis, rare megakaryocytes, and severe iron overload. Due to the interplay between infantile diabetes and unexplained cytopenias, genetic analysis was conducted, and a possible pathogenic SLC19A2 mutation was detected, which confirmed the presence of thiamine-responsive megaloblastic anemia syndrome. Oral thiamine at high dosage was initiated, and the hemoglobin level improved with less need for transfusion
Conclusions
Thiamine-responsive megaloblastic anemia should be considered in infants with diabetes and unexplained cytopenias, especially in consanguineous families. Early genetic diagnosis allows targeted therapy, improves hematologic outcomes, and guides long-term surveillance for hearing and other systemic complications.