P-226: Thiamine-responsive megaloblastic anemia syndrome (TRMA) in siblings: case reports
W Bartnikowska, M Tarasiewicz, S Seget, P Jarosz-ChobotAbstract
Introduction
TRMA is a rare autosomal recessive disorder characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Insulin secretion is present but impaired. Early diagnosis is crucial, as appropriate treatment can significantly improve prognosis.
Objectives
To describe the rare familial occurrence of megaloblastic anemia in two siblings and to emphasize the importance of early diagnosis and treatment.
Methods
We present 5 y/o boy and 1 y/o girl, admitted three months apart to the Diabetes Unit due to newly diagnosed diabetes without typical symptoms of hyperglycemia. The father had type 1 diabetes (positive T1D autoantibodies, treated with MDI). Laboratory tests, genetic testing, and imaging diagnostics were performed. Hematology, neurology, and otolaryngology consultations were conducted.
Results
The boy was found to have macrocytic anemia; in OGTT, the 120-minute glucose level was 229 mg/dL, HbA1c 7.8% (confirming the diagnosis of diabetes). Pending results of T1D autoantibodies, treatment with insulin was initiated. Due to negative autoantibodies, the diagnostic workup was extended to include genetic testing. While awaiting the boy’s genetic results, his sister, during evaluation for anemia, was found to have fasting glucose >126 mg/dL twice and HbA1c of 8.5%. In Diabetology Unit, iv. insulin therapy was initiated temporarily, followed by subcutaneous insulin. During hospitalization, the boy’s genetic test results were obtained, revealing mutations in the SLC19A2 gene, consistent with TRMA, leading to the introduction of high-dose thiamine and hematopoietic vitamins in both children, which allowed for insulin discontinuation. Following the diagnosis of diabetes, CGM were initiated in both siblings.
Conclusions
TRMA should be considered in children with megaloblastic anemia and coexisting carbohydrate metabolism disorders or hearing impairment. Early diagnosis and thiamine supplementation improves clinical outcomes, delay the hearing loss, onset of diabetes and reduce insulin requirements.