Primary Autosomal Recessive Distal Renal Tubular Acidosis Caused by a Common HomozygousSLC4A1Mutation in Two Lao Families

Abstract

Primary distal renal tubular acidosis (dRTA) caused by mutations of the SLC4A1 gene, which encodes for erythroid and kidney isoforms of anion exchanger, shows marked difference in inheritance patterns and clinical features in different parts of the world. While the disease shows autosomal dominant inheritance without any red cell morphological abnormalities in the temperate countries, it is almost invariably recessive, and often accompanies red cell morphological abnormalities or hemolytic anemia in the tropics, especially in Southeast Asia. Here, we report three patients with autosomal recessive (AR) dRTA, presenting with typical findings of failure to thrive and rickets, from two unrelated Lao families. The mutational analyses revealed that all three patients harbored the same homozygous SLC4A1 mutation, p.Gly701Asp. Adequate supplementation of alkali and potassium resulted in remarkable improvement of growth retardation and skeletal deformities of the patients. This is the first case report of Lao patients with AR dRTA caused by SLC4A1 mutations.

Molecular Investigation of Iranian Patients Suspected to Hereditary Spherocytosis

“…In family 1, the causative pathogenic variant was found in the ANK1 gene that encodes a 206-kD protein (Ankyrin protein) and is the most common cause of HS (Approximately half of all HS patients) following by SLC4A1 and SPTB genes [7]. The major function of ankyrin is to stabilize the membrane structure by interacting with beta-spectrin, protein 4.2, and band 3 protein and the deficiency of ankyrin protein leads to a decrease in spectrin assembly on the membrane skeleton thus, causes Loss of membrane [15].…”

“…. Five genes correlated with the pathogenesis of HS so far including Ankyrin (ANK1) (most common (7)), α-spectrin (SPTA1), β-spectrin (SPTB), band 3 (SLC4A1) and protein 4.2 (EPB42) that interplay between the erythrocyte membrane and the lipid bilayer [8]. Defects in protein product of these genes, result in loss of vertical junction between cell membrane and lipid bilayer [1].…”

A Pediatric Case of Long-term Untreated Distal Renal Tubular Acidosis

“…However, AR form of dRTA caused by SLC4A1 mutations has been reported mostly from tropical Southeast Asia and other tropical areas, and is therefore called tropical recessive dRTA 11) . We previously reported three Lao patients from two unrelated families with AR dRTA in association with SLC4A1 mutations 12) .…”

A novel SLC4A1 mutation in a child with hereditary spherocytosis and distal renal tubular acidosis

“…To the Editor: Hereditary spherocytosis (HS) is a common inherited hemolytic anemia 1 characterized by a wide clinical heterogeneity, ranging from asymptomatic to chronic or acute severe hemolysis. [2][3][4][5] Distal renal tubular acidosis (dRTA) is a disorder in which excretion of hydrogen ions is impaired, leading to chronic metabolic acidosis. It is usually accompanied by inappropriately high urinary pH, hypokalemia, hypercalciuria, nephrocalcinosis, and/or nephrolithiasis.…”