Hostname: page-component-6766d58669-r8qmj Total loading time: 0 Render date: 2026-05-17T09:03:55.145Z Has data issue: false hasContentIssue false
  • English
  • Français

Audiometric and imaging characteristics of distal renal tubular acidosis and deafness

Published online by Cambridge University Press:  01 August 2007

B Joshua ,
D M Kaplan ,
E Raveh ,
D Lotan  and
Y Anikster
B Joshua
Affiliation:
Department of Otorhinolaryngology & Head and Neck Surgery, Rabin Medical Center, Petah Tiqwa, Israel
D M Kaplan*
Affiliation:
Department of Otorhinolaryngology & Head and Neck Surgery, Soroka Medical Center, Beer Sheva, the Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
E Raveh
Affiliation:
Schnider Children Hospital, Petah Tiqwa, Israel
D Lotan
Affiliation:
Pediatric Nephrology Unit, Safra Pediatric Hospital, Sheba Medical Center, Tel Hashomer, Israel
Y Anikster
Affiliation:
Metabolic Unit, Safra Pediatric Hospital, Sheba Medical Center, Tel Hashomer, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
*
Address for correspondence: Dr Daniel M Kaplan, Dept of Otolaryngology Head – Neck Surgery, Soroka University Medical Center, POB 151, Beer Sheva, Israel. Fax: 972 86403037 E-mail: dankap@bgu.ac.il
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Primary distal renal tubular acidosis with sensorineural hearing loss is a rare autosomal recessive disease, usually caused by mutations in the ATP6V1B1 gene. The aim of this study was to characterise the phenotype of this disease, with emphasis on the auditory findings, in a cohort of Israeli children.

Study design:

Prospective study of five children, from three unrelated families, with distal renal tubular acidosis and bilateral sensorineural hearing loss, with mutations in the ATP6V1B1 gene.

Methods:

The following were collected from patients' medical records: biochemical and renal data, age at distal renal tubular acidosis diagnosis, and age at hearing loss. Hearing loss progression as well as current hearing status were assessed, and high resolution computed tomography of the temporal bone was performed. All patients underwent genetic testing.

Results:

Four patients were diagnosed with distal renal tubular acidosis before the age of six months and one at 24 months. All had the classical findings of low blood pH and inappropriately high urine pH. Hearing loss was diagnosed between the ages of three months and two years. The hearing loss was bilateral, asymmetrical and progressive, occasionally with a conductive component. Two children underwent cochlear implantation, at ages 10 and 15 years. High resolution computed tomography, performed in four patients between the ages of 2.5 and 15 years, showed bilaterally enlarged vestibular aqueducts. This was the only radiological abnormality in the inner ear in all cases. A different mutation in the ATP6V1B1 gene was found in each family.

Conclusion:

Several types of mutations in the ATP6V1B1 gene may cause distal renal tubular acidosis and sensorineural hearing loss. Patients display a typical progressive type of hearing loss and have enlarged vestibular aqueducts, with no other abnormalities being observed on imaging.

Keywords

DeafnessDistal Renal Tubular AcidosisEnlarged Vestibular AqueductSensorineural Hearing Loss

Information

Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 122 , Issue 2 , February 2008 , pp. 193 - 198
Copyright
Copyright © JLO (1984) Limited 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1 Alper, SL. Genetic diseases of acid-base transporters. Annu Rev Physiol 2002;64:899–2CrossRefGoogle ScholarPubMed
2 Karet, FE, Finberg, KE, Nelson, RD, Nayir, A, Mocan, H, Sanjad, SA et al. Mutations in the gene encoding B1 subunit of H+ -ATPase cause renal tubular acidosis with sensorineural deafness. Nat Genet 1999;21:84–90CrossRefGoogle ScholarPubMed
3 Stover, EH, Borthwick, KJ, Bavalia, C, Eady, N, Fritz, DM, Rungroj, N et al. Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. J Med Genet 2002;39:796–803CrossRefGoogle ScholarPubMed
4 Ruf, R, Rensing, C, Topaloglu, R, Guay-Woodford, L, Klein, C, Vollmer, M et al. Confirmation of the ATP6B1 gene as responsible for distal renal tubular acidosis. Pediatr Nephrol 2003;18:105–9CrossRefGoogle ScholarPubMed
5 Smith, AN, Skaug, J, Choate, KA, Nayir, A, Bakkaloglu, A, Ozen, S et al. Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing. Nat Genet 2000;26:71–5CrossRefGoogle ScholarPubMed
6 Dou, H, Finberg, K, Cardell, EL, Lifton, R, Choo, D. Mice lacking the B1 subunit of H+ -ATPase have normal hearing. Hear Res 2003;180:76–84CrossRefGoogle ScholarPubMed
7 Herak-Kramberger, CM, Breton, S, Brown, D, Kraus, O, Sabolic, I. Distribution of the vacuolar H+ -ATPase along the rat and human male reproductive tract. Biol Reprod 2001;64:1699–707CrossRefGoogle ScholarPubMed
8 Berrettini, S, Forli, F, Franceschini, SS, Ravecca, F, Massimetti, M, Neri, E. Distal renal tubular acidosis associated with isolated large vestibular aqueduct and sensorineural hearing loss. Ann Otol Rhinol Laryngol 2002;111:385–91CrossRefGoogle ScholarPubMed
9 Shinjo, Y, Kaga, K, Igarashi, T. Distal renal tubular acidosis associated with large vestibular aqueduct and sensorineural hearing loss. Acta Otolaryngol 2005;125:667–70CrossRefGoogle ScholarPubMed
10 Borthwick, KJ, Kandemir, N, Topaloglu, R, Kornak, U, Bakkaloglu, A, Yordam, N. A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. J Med Genet 2003;40:115–21CrossRefGoogle ScholarPubMed
11 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;41:238–43CrossRefGoogle ScholarPubMed
12 Forgac, M. Structure and properties of the vacuolar (H+) -ATPases. J Biol Chem 1999;274:12951–4CrossRefGoogle ScholarPubMed
13 Finberg, KE, Wagner, CA, Stehberger, PA, Geibel, JP, Lifton, RP. Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+ -ATPase B1-subunit. Gene 2003;318:25–34CrossRefGoogle ScholarPubMed
14 Couloigner, V, Teixeira, M, Hulin, P, Sterkers, O, Bichara, M, Escoubet, B et al. Effect of locally applied drugs on the pH of luminal fluid in the endolymphatic sac of guinea pig. Am J Physiol Regul Integr Comp Physiol 2000;279:R1695–R1700CrossRefGoogle Scholar
15 Mondini, C. Anatomical section about the congenital deaf, commentaries of the Institute and Academy of Sciences and Arts of Bologna [in Italian]. Bonaniae 1791;7:419–28Google Scholar
16 Valvassori, GE, Clemis, JD. The large vestibular aqueduct syndrome. Laryngoscope 1978;88:723–8CrossRefGoogle ScholarPubMed
17 Levenson, MJ, Parisier, SC, Jacobs, M, Edelstein, DR. The large vestibular aqueduct syndrome in children. A review of 12 cases and the description of a new clinical entity. Arch Otolaryngol Head Neck Surg 1989;115:54–8CrossRefGoogle ScholarPubMed
18 Jackler, RK, De La Cruz, A. The large vestibular aqueduct syndrome. Laryngoscope 1989;99:1238–42CrossRefGoogle ScholarPubMed
19 Pyle, GM. Embryological development and large vestibular aqueduct syndrome. Laryngoscope 2000;110:1837–42CrossRefGoogle ScholarPubMed
20 Davidson, HC, Harnsberger, HR, Lemmerling, MM, Mancuso, AA, White, DK, Tong, KA et al. MR evaluation of vestibulocochlear anomalies associated with large endolymphatic duct and sac. Am J Neuroradiol 1999;20:1435–41Google ScholarPubMed
21 Phelps, PD, Coffey, RA, Trembath, RC, Luxon, LM, Grossman, AB, Britton, KE et al. Radiological malformations of the ear in Pendred syndrome. Clin Radiol 1998;53:268–73CrossRefGoogle ScholarPubMed
22 Goldfeld, M, Glaser, B, Nassir, E, Gomori, JM, Hazani, E, Bishara, N. CT of the ear in Pendred syndrome. Radiology 2005;235:537–40CrossRefGoogle ScholarPubMed
23 Chen, A, Francis, M, Ni, L, Cremers, CW, Kimberling, WJ, Sato, Y et al. Phenotypic manifestations of branchiootorenal syndrome. Am J Med Genet 1995;58:365–70CrossRefGoogle Scholar
24 Everett, LA, Glaser, B, Beck, JC, Idol, JR, Buchs, A, Heyman, M et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–22CrossRefGoogle Scholar
25 Kalatzis, V, Sahly, I, El-Amraoui, A, Petit, C. Eya1 expression in the developing ear and kidney: towards the understanding of the pathogenesis of branchio-oto-renal (BOR) syndrome. Dev Dyn 1998;213:486–993.0.CO;2-L>CrossRefGoogle ScholarPubMed
26 Dou, H, Xu, J, Wang, Z, Smith, AN, Soleimani, M, Karet, FE et al. Co-expression of pendrin, vacuolar H+ -ATPase alpha4-subunit and carbonic anhydrase II in epithelial cells of the murine endolymphatic sac. J Histochem Cytochem 2004;52:1377–84Google ScholarPubMed
27 Royaux, IE, Suzuki, K, Mori, A, Katoh, R, Everett, LA, Kohn, LD et al. Pendrin, the protein encoded by the Pendred syndrome gene (PDS), is an apical porter of iodide in the thyroid and is regulated by thyroglobulin in FRTL-5 cells. Endocrinology 2000;141:839–45CrossRefGoogle ScholarPubMed
28 Yoshino, T, Sato, E, Nakashima, T, Nakashima, W, Teranishi, MA, Nakayama, A et al. The immunohistochemical analysis of pendrin in the mouse inner ear. Hear Res 2004;195:9–16CrossRefGoogle ScholarPubMed
29 Usami, S, Abe, S, Weston, MD, Shinkawa, H, Van Camp, G, Kimberling, WJ. Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations. Hum Genet 1999;104:188–92CrossRefGoogle ScholarPubMed
30 Tsukamoto, K, Suzuki, H, Harada, D, Namba, A, Abe, S, Usami, S. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Eur J Hum Genet 2003;11:916–22CrossRefGoogle ScholarPubMed
31 Pryor, SP, Madeo, AC, Reynolds, JC, Sarlis, NJ, Arnos, KS, Nance, WE et al. SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities. J Med Genet 2005;42:159–65CrossRefGoogle ScholarPubMed
32 Park, HJ, Lee, SJ, Jin, HS, Lee, JO, Go, SH, Jang, HS et al. Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans. Clin Genet 2005;67:160–5CrossRefGoogle ScholarPubMed
33 Wu, CC, Yeh, TH, Chen, PJ, Hsu, CJ. Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation. Laryngoscope 2005;115:1060–4CrossRefGoogle ScholarPubMed
34 Lin, CY, Lin, SL, Kao, CC, Wu, JL. The remediation of hearing deterioration in children with large vestibular aqueduct syndrome. Auris Nasus Larynx 2005;32:99–105CrossRefGoogle ScholarPubMed