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AE1 mutations associated with dominant hereditary spherocytic and stomatocytic http://www.selleckchem.com/products/epz-5676.html anemias are generally unassociated with a renal phenotype. Conversely, dRTA mutations associated with dominant and recessive dRTA were long believed to be without associated erythroid phenotype [1]. However, compound heterozygotes have been described with combined spherostomatocytic anemia and dRTA [2]. More recently, subclinical cation-leak stomatocytosis has been associated with AE1 mutation-associated dRTA [3]. Case reports of nonsporadic dRTA have appeared from India. Among 40 pediatric nephrocalcinosis cases from New Delhi, 50% presented with dRTA between ages 3 and 6 years [4]. However, molecular diagnoses of dRTA have only recently begun to appear from India. A 12-year-old with osteopetrosis, renal tubular acidosis, and cerebral calcifications was homozygous for the carbonic anhydrase II mutation S29P [5], and siblings with dRTA and sensorineural deafness were homozygous for R31X truncations in the B1 subunit of vacuolar H+-ATPase [6]. We report here the first two cases of dRTA from India associated withmutations in the SLC4A1/AE1 gene. Two unrelated patients from Maharashtra with combined hemolytic anemia and dRTA were found to be homozygous for the AE1 A858D mutation, previously detected only in the heterozygous or compound heterozygous state. Patient 1, a 15-year-old from Maharasthtra of Kunbi caste born of a nonconsanguinous marriage, presented at age 6 years with growth retardation, jaundice, and a history of fracture on falling. Physical exam http://www.selleck.cn/products/Staurosporine.html revealed a weight of 13 kg ( http://www.selleckchem.com/products/ly2109761.html age) and rickets. Abdominal sonogram revealed splenomegaly, bilateral renal medullary calcification, and two simple left renal cortical cysts (unchanged 3 years later). Additional findings of ��metabolic acidosis with alkaline urine pH�� (detailed medical records are unavailable) led to the clinical diagnosis of distal renal tubular acidosis. Treatment with oral sodium bicarbonate and potassium citrate reportedly resolved the acidosis. In May 2009, the patient presented with jaundice and history of a recent blood transfusion. Exam revealed normal stature and weight with persistent splenomegaly. Peripheral blood smear revealed ovalocytes and tear drop cells without stomatocytes (Fig. 1A). Hematological indices revealed macrocytic anemia with Hct 13.2%, Hgb 4.9 g/dL, reticulocyte count 7%, mean corpuscular volume 129 fL, mean corpuscular hemoglobin concentration 37.1 g/dL, and relative density width 27.2. Eosin 5��-maleimide (E5M) mean channel fluorescence (MCF) indicating AE1/Band3 surface abundance was 850 au (normal range 1,080�C1,300 au). Serum Vitamin B12 was low at 110 pg/mL (normal range 211�C911 pg/mL). Total bilirubin was 4.9 mg/dL with indirect bilirubin 4.7 mg/dL, and serum alkaline phosphatase was elevated at 530 IU/L. Serum K+ was normal at 4.1 mM. Serum bicarbonate was 26.7 mM with blood pH 7.