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Summary:We report the first successful use of BMT for the treatment of RBC pyruvate kinase (PK) deficiency in a boy who developed neonatal jaundice and severe transfusion-dependent hemolytic anemia a few months after birth. He received a BMT at the age of 5 from an HLAidentical sister who has normal PK activity after conditioning with busulfan and cyclophosphamide. The post-transplant course was uneventful. At present, 3 years after transplant, he is 8 years old and has a normal hemoglobin level and normal RBC PK activity without evidence of hemolysis. DNA analysis has confirmed full engraftment. Bone Marrow Transplantation (2000) 26, 689-690. Keywords: BMT; PK deficiency; pyruvate kinase; stem cell transplantation; DNA-short tandem repeat markers; enzymopathies Pyruvate kinase (PK) deficiency is the most common hereditary RBC enzymopathy of the glycolytic pathway. To date, nearly 400 patients have been reported. 1 The clinical manifestations of PK deficiency are heterogenous, ranging from fetal anemia, neonatal jaundice, severe chronic hemolytic anemia to a fully compensated hemolytic anemia. [1][2][3] Treatment of this disease is mostly symptomatic, including blood transfusion and splenectomy. 1 Bone marrow transplantation has been used to cure the disease in mice and dogs. [4][5][6] In humans, gene transfer of human PK cDNA has been attempted. 7 We briefly reported the first successful use of BMT for the treatment of PK deficiency in a boy who had severe chronic hemolytic anemia from birth. 8 This report describes this case in detail, with long-term follow-up. Case reportThe patient was the product of uneventful pregnancy delivered by caesarean section because of a previous caesarean. His birth weight was 3.2 kg and 12 h after birth, pallor and jaundice were noticed. The Hb was 9.6 g/dl, reticulocytes 9.6%, RBC morphology revealed mild hypochromia, anisocytosis, poikilocytosis, polychromasia and the presence of 445 nucleated RBC per 100 WBC. The mother was blood group 'O' and the patient blood group 'B'. His bilirubin level was 14.9 mg/dl. Blood group 'B-O' incompatibility was diagnosed and an exchange blood transfusion was given on the second day of life followed by phototherapy for a few days. He was sent home at the age of 7 days.At the age of 4 months, he was markedly anemic with a Hb level of 5.5 g/dl. RBC glucose-6-phosphate dehydrogenase (G-6-PD) was normal and Hb typing revealed E F A (21.7, 13.1, 65.2%). Several packed red cell transfusions were given to improve symptoms of anemia. At the age of 13 months mild hepatosplenomegaly was noted with a Hb level of 6 g/dl. He was diagnosed at the age of 3 years as having PK deficiency and Hb E trait. His father was heterozygous for both Hb E and PK deficiency, his mother was heterozygous for PK deficiency and his elder sister had Hb E trait but normal red blood cell PK activity. 9 Since he was markedly anemic and the spleen was getting larger, he received hypertransfusion and iron chelation at the age of 3 years. His Hb was maintained above 10 g/dl with an ...

Anion exchanger 1 (AE1 or SLC4A1) mutations have been reported to cause distal renal tubular acidosis (dRTA), a disease characterized by impaired acid excretion in the distal nephron. We have recently demonstrated homozygous AE1 G701D mutation as a common molecular defect of autosomal recessive (AR) dRTA in a group of Thai pediatric patients. In the present work, we discovered a de novo heterozygous AE1 R589C mutation, previously documented in inherited autosomal dominant (AD) dRTA. Arginine at this position is conserved in all vertebrate AE proteins indicating its functional importance. Three different mutations at this position (R589C, R589H, and R589S) were all found in AD dRTA and a de novo R589H mutation has previously been recorded. Our report is the second de novo mutation but with a different substituted amino acid. A high prevalence of AE1 R589 mutations and the presence of at least two de novo mutations at this position lead us to propose that codon 589 (CGC) is a "mutational hotspot" of AE1. The mechanism of recurrent mutations probably involves methylation and deamination altering cytosine (C) to thymine (T) in the CpG dinucleotides.A de novo R589C mutation of anion exchanger 1 causing distal renal tubular acidosis

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