Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 552 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

Table of Contents   
CASE REPORT  
Year : 2015  |  Volume : 26  |  Issue : 1  |  Page : 119-121
Distal renal tubular acidosis with nerve deafness secondary to ATP6B1 gene mutation


1 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Sri Venkateswara University, Tirupati, India
2 Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences, Sri Venkateswara University, Tirupati, India

Click here for correspondence address and email

Date of Web Publication8-Jan-2015
 

   Abstract 

Autosomal recessive distal renal tubular acidosis (dRTA) is associated with mutation in the ATP6B1 gene encoding the B1 subunit of H + -ATPase, one of the key membrane transporters for net acid excretion of α-intercalated cells of medullary collecting ducts. Sensori-neural deafness frequently accompanies this type of dRTA. We herewith describe a patient who had distinct features of dRTA with bilateral sensori-neural hearing loss and ATP6B1 mutation. This is a rare entity.

How to cite this article:
Naveen PS, Srikanth L, Venkatesh K, Sarma PG, Sridhar N, Krishnakishore C, Sandeep Y, Manjusha Y, Sivakumar V. Distal renal tubular acidosis with nerve deafness secondary to ATP6B1 gene mutation. Saudi J Kidney Dis Transpl 2015;26:119-21

How to cite this URL:
Naveen PS, Srikanth L, Venkatesh K, Sarma PG, Sridhar N, Krishnakishore C, Sandeep Y, Manjusha Y, Sivakumar V. Distal renal tubular acidosis with nerve deafness secondary to ATP6B1 gene mutation. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Feb 27];26:119-21. Available from: https://www.sjkdt.org/text.asp?2015/26/1/119/148757

   Introduction Top


Distal renal tubular acidosis (dRTA) may occur in two forms, acquired and inherited. Inherited RTA can be autosomal dominant (AD) or autosomal recessive (AR). AR dRTA may be associated with mutation in the ATP6B1 gene encoding the B1 subunit of H + ATPase. H + -ATPase is one of the key membrane transporters for net acid secretion in the α intercalated cells of the medullary collecting ducts. Interestingly, sensori-neural hearing loss frequently accompanies this type of dRTA. [1],[2] We present herein one such patient who had a combination of dRTA with bilateral sensorineural hearing loss.


   Case Report Top


A 13-year-old male was referred for evaluation of hypokalemia. He is the third child born to a second-degree consanguineous couple. He was born at the 40 th week of gestation with a birth weight of 3 kg. He was found to have a hearing defect from birth, with delay in development of language. On evaluation, he was found to have the following: Weight 25 kg, height 132 cm (both below the 3 rd percentile), widening of both wrists, pectus carinatum, beading of ribs and bilateral genu valgum. Investigations were as follows: Urine pH 7.5, no pyuria, hematuria or glycosuria, hemoglobin 12.3 g/L, serum creatinine 0.6 mg/dL, blood urea 14 mg/dL, serum sodium 137 meq/L, serum potassium 2.8 meq/L, serum calcium 9.4 mg/dL, serum phosphorus 3.2 mg/dL, serum chloride 111 mmol/L, serum albumin 42 g/L and serum alkaline phosphatase 706 IU/L. Urinary parameters were as follows: 24-h protein 430 mg/day, sodium 310 mEq/day, potassium 77 mEq/day, phosphorus 560 mg/day, calcium 180 mg/day and uric acid 460 mg/day. Arterial blood gas showed pH of 7.39, bicarbonate of 13.6 mEq/L and PaCO 2 of 22.6 mm Hg. Ultrasound of the abdomen showed bilateral medullary nephro-calcinosis. Audiometry was suggestive of sensori-neural deafness. Genetic analysis was positive for ATP6B1 gene mutation [Figure 1], which was performed after taking consent from his parents. The study could not be extended to other members of the family as they declined to participate.
Figure 1: PCR amplification of exon 3 4, ATP6B1 GENE.

Click here to view



   Discussion Top


Acid base homeostasis is critical for normal cellular function, growth and development. The kidney plays an important role in maintenance of long-term acid-base balance through a coupled process of bicarbonate reabsorption and acid secretion. In adults, the kidney normally filters and reabsorbs about 4500 mmols of bicarbonate per day and also achieves net secretion of approximately 70 mmols of H + produced from the normal catabolism as nonvolatile acid. The net acid secretion is mediated largely by the energy-dependent proton pump located in the apical membrane of αintercalated cells of distal nephron and is linked to bicarbonate absorption across the basolateral membrane of the cells. Failure of the urine acidification process results in dRTA, which is characterized by metabolic acidosis of varying severity accompanied by inappropriate alkaline urine. [1],[2]

RTA may be inherited or acquired. The inherited variety is genetically heterozygous and dRTA can be transmitted as AD or AR trait. AR dRTA is associated with mutation in the ATP6B1 gene encoding the B 1 sub-unit of H + -ATPase. H + -ATPase is one of the key membrane transporters for net acid excretion in the α-intercalated cells of the medullary collecting duct. H + -ATPase is a long heterooligomeric complex present in both cytosol and transmembrane domains (cytosolic V 1 domain and transmembrane V 0 domain). The B subunit belongs to the V 1 domain and has two isoforms, B 1 and B 2 . The B 1 subunit is present in the intercalated cells, whereas the B 2 subunit is absent in the intercalated cells. [1],[2] Sensori-neural hearing loss frequently accompanies AR dRTA associated with mutation in the ATP6B1 gene encoding the B 1 sub-unit of H + ATPase. An active acidification process constantly occurs in the ear to maintain endo-lymph pH near 7.4 in the cochlea and closer to 6.6 in the endo-lymphatic sac. The sensori-neural deafness is attributed to mutation of ATP6B1, which in turn shows its effects through the B1 subunit, mediating H + -ATPase function. [1],[2],[3],[4],[5] However, systemic alkalinization, although found to result in normal acid balance and normal growth, fails to improve abnormalities in auditory function. [1],[4]

In our patient, the dRTA was diagnosed by the presence of metabolic acidosis and inappropriate alkaline urine (urine pH >5.5 in the presence of systemic acidosis) with normal anion gap. In addition, he was underweight with growth retardation and nephrocalcinosis. He was also found to have bilateral sensorineural deafness on audiometry evaluation. Mutational analysis showed distinct ATP6B1 mutation, corroborating the results reported by Karet et al. [3] They have shown distinct ATP6B1 mutation being present in chromosome 2p13 encoding the B1 subunit of the vacuolar H + ATPase in the distal tubule. Sensori-neural hearing loss is another frequently accompanying feature within ATP6B1 mutations. [1],[3]

Using polyclonal antibodies raised against ATP6B1, Karet et al showed the expression of ATP6B1 in the cochlea and endo-lymphatic sac; they also showed intense staining of the B1 sub-unit in the inter-dental cell layer of the cochlear spiral limbus and in the epithelial cells of the endo-lymphatic sac. These observations suggest that ATP6B1 plays an important role in the endo-lymph pH homeostasis and normal auditory function. [2],[3]

This case is reported in view of its rarity and demonstrable abnormality in the ATP6B1 gene encoding the B1 subunit H + -ATPase, manifesting as dRTA with sensori-neural deafness.

Conflict of interest: None

 
   References Top

1.
Hahn H, Kang HG, Ha IS, Cheong HI, Choi Y. ATP6B1 gene mutations associated with distal renal tubular acidosis and deafness in a child. Am J Kidney Dis 2003;41:238-43.  Back to cited text no. 1
    
2.
Gil H, Santos F, García E, et al. Distal RTA with nerve deafness: Clinical spectrum and mutational analysis in five children. Pediatr Nephrol 2007;22:825-8.  Back to cited text no. 2
    
3.
Karet FE, Finberg KE, Nelson RD, et al. Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness. Nat Genet 1999;21:84-90.  Back to cited text no. 3
    
4.
Rodríguez-Soriano J. New insights into the pathogenesis of renal tubular acidosis from functional to molecular studies. Pediatr Nephrol 2000;14:1121-36.  Back to cited text no. 4
    
5.
Batlle D, Ghanekar H, Jain S, Mitra A. Hereditary distal renal tubular acidosis: New Understandings. Annu Rev Med 2001;52:471-84.  Back to cited text no. 5
    

Top
Correspondence Address:
Dr. Vishnubhotla Sivakumar
Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Sri Venkateswara University, Tirupati
India
Login to access the Email id


DOI: 10.4103/1319-2442.148757

PMID: 25579729

Rights and Permissions


    Figures

  [Figure 1]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Case Report
   Discussion
    References
    Article Figures
 

 Article Access Statistics
    Viewed1850    
    Printed29    
    Emailed0    
    PDF Downloaded373    
    Comments [Add]    

Recommend this journal