Beta-Thalassemia Minor Is Associated with IgA Nephropathy

Thalassemia refers to a group of hereditary diseases caused by a defect in alpha or beta globin synthesis [1]. This impaired synthesis leads to a reduced supply of globin chains and results in the malformation of hemoglobin, which gives rise to microcytic hypochromic anemia. However, since synthesis of the unaffected globin occurs at a normal rate, the alpha or beta subunits accumulate disproportionately. Consequently, inclusions lead to the destruction of erythroblasts in the bone marrow, and hemolytic anemia results as the surviving cells are cleared in the spleen [1, 2]. Thalassemia is most prevalent in the Mediterranean region, in countries such as Greece, Turkey, and Italy, in addition to Southeast Asia and North Africa. Although its occurrence is currently rare in Korea, it is expected to increase as a result of the surge in migration from Southeast Asia to Korea, experienced since the 1990s. Microscopic hematuria is frequently observed in thalassemia patients, and is considered to be the result of tubular damage induced by iron deposition, hypercalciuria, hyperuricosuria, and deferoxamine. However, the existence and extent of tubular damage have not been thoroughly evaluated by renal biopsy. On the other hand, glomerulonephritis has not been considered to be a main cause of microscopic hematuria in thalassemia. Here, we report a 70-yr-old Korean man who was diagnosed with beta-thalassemia minor that was associated with IgA nephropathy and complicated by microscopic hematuria and the progression of renal failure. The patient had been diagnosed with anemia 10 yr earlier; follow-up had not included any further diagnostic studies or specific treatment. Hematologic tests revealed microcytic hypochromic anemia: Hb, 9.9 g/dL; hematocrit, 31.4%; mean corpuscular volume, 58.3 fL; mean corpuscular Hb, 18.4 pg; mean corpuscular Hb concentration, 31.5 g/dL. Peripheral blood smear showed anisocytosis, poikilocytosis (target cells), and basophilic stippling. Bone marrow examination revealed normocellular marrow with erythroid hyperplasia but no ringed sideroblasts (Fig. 1). Hb electrophoresis showed a normal pattern: 98.3% Hb A and 1.7% Hb A2. Since the morphologic abnormalities detected in the peripheral blood smear and the bone marrow examination were associated with impaired Hb synthesis, thalassemia was suspected. We confirmed the absence of interracial marriages in his family history based on pedigree analysis. Consequently, the globin genes were analyzed, and all exons and introns of the Hb beta (HBB) gene, which is the causal gene of beta-thalassemia located on chromosome 11p15.5, were sequenced. Subsequently, a heterozygous substitution mutation was discovered in the ATG initiation codon, which changed it to AGG. Therefore, a final diagnosis of beta-thalassemia minor was confirmed. The patient did not have any history of transfusion or deferoxamine use. During follow-up, the patient showed persistent microscopic hematuria with new-onset overt proteinuria and progression of