ESPE Abstracts

Background: Thiamine-responsive megaloblastic anemia (TRMA) syndrome, is an autosomal recessive disorder marked by sensorineural hearing loss, diabetes mellitus, and megaloblastic anemia caused by mutations in the SLC19A2 gene.

Objective: We are reporting five patients with TRMA syndrome in the Pakistani population.

Case Summary: We report five male patients, from two different families, born to consanguineous parents, ages 14 months, 2, 8, and 12 years, presented at the Children’s Hospital Lahore, Pakistan. These patients were initially diagnosed with insulin-dependent type 1 diabetes and put on a basal-bolus insulin regime. Later, these patients presented with progressive pallor and were on recurrent blood transfusions. Parents also noticed that they had a hearing problem that worsened with passage of time. There was no history of visual disturbance or difficulty walking. On examination, they were not dysmorphic, with height and weight below 5th centile. The systemic examination was unremarkable. All patients were developmentally normal. The mean age of children was 6.08 ± 4.42, with mean haemoglobin levels of 7.38 ± 1.36, mean MCV of 97.60 ± 4.87, and mean HbA1c of 9.70 ± 1.28. Patient (age 2 years) had pancytopenia with haemoglobin 6.5 g/dl, RBC count 3.10 × 10¹²/L, MCV 97 Fl, TLC 3.3 × 10⁹/L, Platelets 60 × 10⁹/L, Retic count 0.4 %. Bone marrow examination showed a megaloblastic picture with ring sideroblast and no atypical cells. All patients have normal ferritin, vitamin B12, and folic acid levels with negative thyroid and celiac screenings. Urine and blood osmolality were normal. Hearing assessments revealed moderate to severe sensorineural hearing loss and advised hearing aids. Due to suspicion of TRMA, patients were put on Tab. Thiamine with age-appropriate dosing. After the thiamine treatment, there was a marked improvement in glycemic control, with a reduction in insulin requirements and HbA1c levels (p-value 0.001). With time, a complete blood count showed improvement in hemoglobin levels (p-value 0.003) with normalization of the MCV, leucocyte count and platelet count without any transfusion. These outcomes strengthen our diagnosis of TRMA. Due to financial restraints, we are unable to do genetic testing for confirmation of SLC19A2 gene mutations.

Conclusion: In this case series, one patient presented with pancytopenia, which is a very rare presentation of TRMA syndrome, and few cases have been reported previously. These case studies emphasise the importance of thiamine treatment and early diagnosis in children who come with anemia, diabetes, and deafness, particularly in this region of the world where there is a significant background consanguinity.

Keywords: Megaloblastic anemia, deafness, TRMA