THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME: A NOVEL MUTATION

Summary.Thianiine-rexponsive megaloblastic anemia syndrome: a novel mutation: The thiaminc-responsive megaloblastic anemia syndrome (TRMA) is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural hearing loss due to mutations in SLC 1 9A2 that encodes a thiamine transporter protein. The disease can manifest at any time between infancy and adolescence, and not all cardinal findings are present initially. The anemia typically improves significantly with pharmacological doses of thiamine. Variable improvement in diabetes is also noted. However, the hearing loss is apparently irreversible, although a delay in the onset of deafness may be possible. We present a 2-year old girl with non-autoimmune diabetes mellitus and anemia in whom we found a novelc.95T>A (leu32X) mutation in the SLC19A2 gene in this study.Our patient with this new mutation did not suffer from hearing loss. Key-words: Thiamme-responsive megaloblastic anemia - Non-autoimmune diabetes - Hearing loss - New mutation. INTRODUCTION The thiamine-responsive megaloblastic anemia syndrome (TRMA), also called Rogers Syndrome, is a very rare syndrome characterized by early onset diabetes mellitus, megaloblastic anemia and sensorineural hearing loss (18). In addition to the cardinal components, other findings reported in association with the TRMA syndrome include congenital heart disease, arrhythmias, cardiomyopathy, retinal degeneration, optic atrophy, situs inversus, aminoaciduria, stroke and atrial standstill (2,4,19,20). The disease can manifest at any time between infancy and adolescence, and all the cardinal findings are often not present initially (15). Anemia typically improves significantly with pharmacological doses of thiamine (25-75 mg/day), although the erythrocytes remain macrocytic. Variable improvement in diabetes is also noted. However, the hearing loss is apparently irreversible, although a delay in the onset of deafness may be possible (5). We present a 2-year-old girl with non-autoimmune diabetes mellitus and anemia where we found a previously undefined c.95T>A (leu32X) mutation in the SLC19A2 gene in this study. Defining new mutations for this rare syndrome will increase experience with genotype-phenotype correlation and contribute to the future development of treatment methods. CASE REPORT A 2-year-old girl presented with fever and cough to another hospital and was diagnosed with pneumonia. At that time, she was found to be hyperglycemic (serum glucose 300 mg/dl). She was diagnosed with diabetes mellitus and was treated with insulin. Her initial insulin dose was progressively increased to 2 U/kg/day due to infection. She came to our hospital after pneumonia treatment. She was still on insulin at a dose of 0.5 U/kg/day. She had been born as the second child of consanguineous Turkish parents. The parents and a female sibling were healthy. On physical examination, her height was 88 cm (50-75* percentile) and weight 12 kg (50,h percentile). She could hear and talk normally. Physical examination was normal except for a grade I/Vl systolic, ejection-type murmur. Laboratory findings included an elevated glycosylated hemoglobin Ale concentration of 7%, negative anti-insulin, anti-GAD and antiislet cell antibodies, plasma C-peptide of 1 .06 ng/ml (0.5 - 4 ng/ml), hemoglobin levelof 9.2 g /dL, MCV of 94 fL, hematocrit of 29.2%, platelet count of 1 78,000/mm' and normal serum ferritin, vitamin B 1 2, and red blood cell folate levels. Peripheral smear showed anisopoikilocytosis with a predominance of macrocytic cells and no hemolytic findings. Echocardiography confirmed an atrial septal defect. The brain stem auditory evoked potentials were bilaterally normal. We diagnosed thiamine-responsive megaloblastic anemia in combination with nonautoimmune diabetes mellitus and cardiac defects but without hearing loss. The serum thiamine level was also found to be decreased at 19. …