PB1977 LATE DIAGNOSIS IN SYRIAN IMMIGRANT PATIENT; THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME

Abstract

Background: Thiamine-responsive megaloblastic anemia (TRMA) also known as Rogers syndrome was first described by Porter et al in 1969. It is characterized by diabetes mellitus, megaloblastic anemia and progressive sensorineural hearing loss. TRMA is a rare autosomal recessive disorder. Aims: This syndrome is seen especially in consanguineous marriages and isolated communities. İt has been reported in fewer than 80 families worldwide. Diagnosis relies on uncovering genetic variations (alleles) in the SLC19A2 gene, encoding for a high affinity thiamine transporter. This transporter is essentially present in hematopoietic stem cells, pancreaticc beta cells and inner ear cells, explaining the clinical manifestations of the disease. The disease is usually diagnosed in childhood period. Methods: We presented a 21-year-old patient who was diagnosed with TRMA with the findings of pancytopenia. Results: Case Report: A 21-year-old male patient was referred to our center upon the symptoms of fatigue, hearing loss and pancytopenia. He was emigrated from Syria to Turkey for years ago because of the Syrian War. Mother and father are first-degree relatives. He has hearing loss and inarticulated since hewas 1 year old. He was diagnosed as type 1 diabetes mellitus at 10 years old and treated with insulin. Erythrocyte transfusion had been performed several times due to the anemia. In laboratory tests; Wbc:2480 10^3 /μL, Hgb:4.3 g/dL Plt: 8000 10^3 /μL, MCV:81 fL, Glukoz: 345 mg/dL, Crea1nin:0,7 mg/dL, ldh:92 U/L, Ferri1n:1140 ug/L, VitB12: 702 ng/L, Folat: 5,2 ug/L were found. There was hepatomegaly and splenomegaly in abdominal ultrasonography. Megaloblastic changes were seen in peripheral blood smear, but there was no atypical cells. Bone marrow biopsy and flow cytometric evaluation were normal. Audiologic evaluation showed bilateral severe sensorineural hearing. Considering the laboratory test and clinical findings, a diagnosis of TRMA was suspected and the patient was started on thiamine hydrochloride (100 mg orally daily). An increase in leukocyte and platelet counts was observed on the 5th day of thiamine treatment. On the 10th day of treatment, an increase in hemoglobin level was observed. His pancytopenia was completely resolved. WBC: 7000 10^3 /μL, Hgb: 15 g/dL Plt: 234000 10^3 /μL, mcv: 91 were detected afer two months of treatment. At the same time genetic evaluation was initiated. Homozygous mutation in the SLC19A2 gene (c.242_243insA (p.Y81 ∗) (p.Tyr81 ∗) was detected as a result of genetic evaluation. Summary/Conclusion: Literature showed that the cases of TRMA are mostly diagnosed during childhood period. Our case was diagnosed at the age of 21. He is different from the others with this respect. Pancytopenia has been described several times in Rogers syndrome. There were serious cytopenia in our case at the time of diagnosis. Rapid improvement in cytopenia was seen afer the treatment with thiamine. In conclusion TRMA is a rare autosomal recessive disorder which typically has a clinical triad: megaloblastic anemia, diabetes mellitus and sensorineural hearing loss. Thiamine treatment should be continued for lifelong. Family screening should be done and genetic counseling should be offered when diagnosed.