Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies

Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematologica...

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Main Authors: Sookkasem Khositseth, Apiwan Sirikanaerat, Siri Khoprasert, Sauwalak Opastirakul, Pornchai Kingwatanakul, Wanna Thongnoppakhun, Pa Thai Yenchitsomanus
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Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/60636
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spelling th-cmuir.6653943832-606362018-09-10T03:46:26Z Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies Sookkasem Khositseth Apiwan Sirikanaerat Siri Khoprasert Sauwalak Opastirakul Pornchai Kingwatanakul Wanna Thongnoppakhun Pa Thai Yenchitsomanus Medicine Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous α+-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (- SEA/-α4.2). The blood smears of patients with homozygous G701D/G701D showed ∼25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous α+- thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous α+-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis. © 2008 Wiley-Liss, Inc. 2018-09-10T03:46:26Z 2018-09-10T03:46:26Z 2008-06-01 Journal 10968652 03618609 2-s2.0-41949103722 10.1002/ajh.21151 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=41949103722&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/60636
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Medicine
spellingShingle Medicine
Sookkasem Khositseth
Apiwan Sirikanaerat
Siri Khoprasert
Sauwalak Opastirakul
Pornchai Kingwatanakul
Wanna Thongnoppakhun
Pa Thai Yenchitsomanus
Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
description Mutations of the human SLC4A1 gene encoding erythroid and kidney isoforms of anion exchanger 1 (AE1, band 3) result in erythrocyte abnormalities or distal renal tubular acidosis (dRTA) and such mutations are observed in Southeast Asia, where hemoglobinopathies are prevalent. Genetic and hematological studies in 18 Thai patients with dRTA have shown that 12 of them (67%) carried SLC4A1 mutations (7 G701D/G701D, 3 SAO/G701D, and 2 G701D/A858D). Of these 12 patients, three had homozygous G701D/G701D and heterozygous Hb E; one compound heterozygous SAO/G701D and heterozygous α+-thalassemia; and one compound heterozygous G701D/A858D and heterozygous Hb E. Of 6 patients without SLC4A1 mutation, two each carried heterozygous or homozygous Hb E and one of the latter also had Hb H disease (- SEA/-α4.2). The blood smears of patients with homozygous G701D/G701D showed ∼25% ovalocytes. Strikingly, the patients with coexistence of homozygous G701D/G701D and heterozygous Hb E had 58% ovalocytes. Similarly, the patients who had compound heterozygous SAO/G701D showed 49% ovalocytes, but the patient with coexistence of compound heterozygous SAO/G701D and heterozygous α+- thalassemia had 70% ovalocytes. Our previous study has shown that under metabolic acidosis, the patients with homozygous G701D/G701D or compound heterozygous SAO/G701D had reticulocytosis, indicating compensated hemolysis. A patient with compound heterozygous SAO/G701D and heterozygous α+-thalassemia presented with hemolytic anemia and hepatosplenomegaly which was alleviated by alkaline therapy. Taken together, the coexistence of both homozygous or compound heterozygous SLC4A1 mutations and hemoglobinopathy has a combined effect on red cell morphology and degree of hemolytic anemia, which is aggravated by acidosis. © 2008 Wiley-Liss, Inc.
format Journal
author Sookkasem Khositseth
Apiwan Sirikanaerat
Siri Khoprasert
Sauwalak Opastirakul
Pornchai Kingwatanakul
Wanna Thongnoppakhun
Pa Thai Yenchitsomanus
author_facet Sookkasem Khositseth
Apiwan Sirikanaerat
Siri Khoprasert
Sauwalak Opastirakul
Pornchai Kingwatanakul
Wanna Thongnoppakhun
Pa Thai Yenchitsomanus
author_sort Sookkasem Khositseth
title Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
title_short Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
title_full Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
title_fullStr Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
title_full_unstemmed Hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
title_sort hematological abnormalities in patients with distal renal tubular acidosis and hemoglobinopathies
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=41949103722&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/60636
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