High prevalence of Southeast Asian ovalocytosis in Malays with distal renal tubular acidosis

Abstract

Southeast Asian ovalocytosis (SAO) is a red blood cell abnormality common in malaria-endemic regions and caused by a 27 nt deletion of the band 3 protein gene. Since band 3 protein, also known as anion exchanger 1, is expressed in renal distal tubules, the incidence of SAO was examined in distal renal tubular acidosis (dRTA) in Malays in Kelantan, Malaysia. Twenty-two patients with dRTA and 50 healthy volunteers were examined for complication of SAO by both morphological and genetic analyses. SAO was identified in 18 of the 22 dRTA patients (81.8%), but only two of the 50 controls (4%). The incidence of SAO was significantly high in those with dRTA (p<0.001), indicating a dysfunctional role for band 3 protein/anion exchanger 1 in the development of dRTA.

Distal Renal Tubular Acidosis in Mice Lacking the AE1 (Band3) Cl−/HCO3 − Exchanger (slc4a1)

“…However, most autosomal recessive dRTA in humans is caused by AE1 mutations that are compatible with normal eAE1 abundance and near-normal eAE1 anion transport function in erythrocytes. These conditional loss-of-function mutations in human AE1 are functionally rescued in erythrocytes by the tissue-specific expression of the AE1-binding protein glycophorin A, which likely functions as both trafficking chaperonin and plasmalemmal subunit of eAE1 (10,14).…”

“…At least two pathophysiologic mechanisms have been proposed to explain autosomal dominant dRTA as a result of AE1 mutations (1,9): A dominant negative intracellular retention phenotype (18) and a dominant or co-dominant mistargeting to the apical membrane (19,20). A distinct set of mutations found among Southeast Asians and Melanesians is transmitted in autosomal or compound recessive patterns (11,14). The recessive disease is often of earlier onset and accompanied by a urinary concentrating defect, with affected infants susceptible to severe dehydration (1,3,5,15,17,(21)(22)(23).…”

Coinheritance of Southeast Asian ovalocytosis and the β-thalassemia trait in a Malay family

“…SAO is frequent in Southeast Asia and Melanesia, occurring in up to 30% of people in some groups [1][2][3][4]. In Malaysia, the incidence of the disorder is estimated to be 4% [5]. Although the exact distribution in different ethnic groups in Malaysia is not known, Eng (1965) reported the incidence of hereditary ovalocytosis to be 12.3% in aborigines of the Senoi tribe of Malaysia [1].…”

“…In the Malaysian population, the prevalence of SAO is around 4% [5]. It is an asymptomatic hereditary autosomal dominant disorder characterized by macro-ovalocytes and stomatocytes constituting 25% of the cells in peripheral blood smears (PBS).…”

Homozygous Southeast Asian hereditary ovalostomatocytosis: Management dilemma

“…Homozygous SAO is hypothesized to be incompatible with life due to a 50% decrease in anion transport. Some suggest that other cell types that rely on the expression of the Band 3 allele during the embryonal stage may not be capable of chloride‐bicarbonate exchange . Homozygous SAO may also lead to extensive aggregation of SAO cells during erythropoiesis that preclude its release from the bone marrow.…”