Renal Tubular Acidosis (RTA)


Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. Distal RTA  is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while K+ cannot be reabsorbed, leading to acidemia (as H+ builds up in the body) and hypokalemia (as K+ cannot be reabsorbed). This leads to the clinical features of distal RTA. This disorder has been classified by four types: Type 1 Distal, Type 2 Proximal, Type 3 Combined Distal and Proximal, and Type 4.

We provide sequencing analysis for the genes listed below that are associated with RTA.

Type OMIM Gene/Protein Description

Renal tubular acidosis, autosomal recessive with osteopetrosis (Type 3, or Juvenille RTA)

259730 CA2/ CA II

CA II protein is encoded by the CA2 gene on chromosome 8q22. The expression of CA II is affected in bone, kidney (in both proximal and distal nephron segments, explaining the mixed acidosis) and the brain. CA2 mutations have been observed in recessive, distal and proximal forms of RTA.

Renal tubular acidosis, distal, autosomal dominant


Rental tubular acidosis, distal, autosomal recessive





SLC4A1 gene encodes the AE1 glycoprotein which is found in red blood cells and the kidneys. Defects in AE1 lead to morphological changes of red blood cells and autosomal dominant distal RTA.

Recent gene studies have shown that some of the AE1 mutations are responsible for autosomal recessive distal RTA in several countries in Southeast Asia.

Renal tubular acidosis, distal, autosomal recessive (dRTA, Type 1)






ATP6V0A4 gene encodes a kidney-specific a4 isoform subunit of H+-ATPase. The involvement of the a4 subunit in distal RTA shows that it is essential for proper proton pump function in the kidneys. Mutations in this gene are observed most often in patients with distal recessive RTA.

Renal tubular acidosis, distal, autosomal recessive with nerve deafness (Type 1b)



Clinical findings, other than deafness, are identical to those present in patients with autosomal recessive distal RTA and normal hearing. Variations in the presentation of deafness, from birth to late childhood, it is progressive and does not respond to alkali therapy.

Renal tubular acidosis, proximal (pRTA, Type 2) 604278 SLC4A4

Proximal RTA is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than  Distal RTA and the urine can acidify to a pH of less than 5.3.

Purpose: Confirmation of Clinical Diagnosis

Methodology: Next-Generation Sequencing

Test Requisition: Sequencing Requisition

Specimen Requirements: 2-5 mL Blood- Lavender Top Tube

Panel CPT Code: 81479x5 Cost: $1500.00

Turn-around-time: 6 weeks

Shipping Information


1. Laing CM, Toye AM, Capasso G, Unwin RJ (2005). "Renal tubular acidosis: developments in our understanding of the molecular basis". Int. J. Biochem. Cell Biol. 37 (6): 1151–61. DOI:10.1016/j.biocel.2005.01.002. PMID 15778079.

2. Vargas-Poussou R, Houillier P, Le Pottier N, Strompf L, et al (2006). “Genetic investigation of autosomal recessive distal renal tubular acidosis: evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene”. J Am Soc Nephrol.17(5):1437-43.

3. Chaabani H, Hadj-Khlil A, Ben-Dhia N,Braham H. et al (1994). “The primary hereditary form of distal renal tubular acidosis: clinical and genetic studies in 60-member kindred”. Clin Genet. 45(4):194-9.

4. Stover EH, Borthwick KJ, Bavalia C, Eady N, et al (2002). “Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss”. J Med Genet. 39(11):796-803.

5. de Jong PE, Koomans HA, Weening JJ (2000). Klinische Nefrologie (3rd ed.). Maarssen: Elsevier. pp. 141–2.

6. Igarashi T, Inatomi J, Sekine T, Cha SH, Kanai Y et al.(1999)"Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities". Nat Genet.23(3):264-6.

7. Rodríguez-Soriano J. (2000). "New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies". Pediatr. Nephrol.14:1121–36.

8. Ring T, Frische S, Nielsen S. (2005). "Clinical review: renal tubular acidosis - a physicochemical approach". Crit. Care. 9:573–580.

9. Karet FE. (2002). "Inherited Distal Renal Tubular Acidosis". J. Am. Soc. Nephrol.13:2178–2184.




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1122 NE 13 Street, Suite 1400, Oklahoma City, OK 73104
Phone: (405) 271-3589 |Fax: (405) 271-7117 Email: Dr. Shibo Li

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