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Distal renal tubular acidosis. Clinical manifestations in patients with different underlying gene mutations

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Abstract

Background

To evaluate whether there are differences in the phenotype of primary distal renal tubular acidosis (dRTA) patients according to the causal defective gene.

Methods

Twenty-seven non-oriental patients with genetically confirmed dRTA were grouped according to the identified underlying mutations in either ATP6V1B1 (n = 10), ATP6V0A4 (n = 12), or SLC4A1 (n = 5) gene. Demographic features, growth impairment, biochemical variables and presence of deafness, nephrocalcinosis, and urolithiasis at diagnosis were compared among the three groups.

Results

Patients with SLC4A1 mutations presented later than those with ATP6V1B1 or ATP6V0A4 defects (120 vs. 7 and 3 months, respectively). Hearing loss at diagnosis was present in the majority of patients with ATP6V1B1 mutations, in two patients with ATP6V0A4 mutations, and in none of cases harboring SLC4A1 mutations. Serum potassium concentration (X ± SD) was higher in SLC4A1 group (3.66 ± 0.44 mEq/L) than in ATP6V0A4 group (2.96 ± 0.63 mEq/L) (p = 0.046). There were no differences in the other clinical or biochemical variables analyzed in the three groups.

Conclusions

This study indicates that non-oriental patients with dRTA caused by mutations in the SLC4A1 gene present later and have normokalemia or milder hypokalemia. Hypoacusia at diagnosis is characteristically associated with ATP6V1B1 gene mutations although it may also be present in infants with ATP6V0A4 defects. Other phenotypical manifestations do not allow predicting the involved gene.

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Abbreviations

dRTA:

distal renal tubular acidosis

ATP6V0A4:

ATPase H+ transporting V0 subunit A4

ATP6V1B1:

ATPase H+ transporting V1 dubunit B1

SLC4A1:

Solute carrier family 4 member 1

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Funding

This work was supported partially by GRUPIN 14-020 grant from “Principado de Asturias” Funds, ISCIII FIS PI14/00702, Plan Estatal I+D+I 2013-2016, FEDER Funds, and FundaciónNutrición y Crecimiento.

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Authors and Affiliations

  1. University of Oviedo, Oviedo, Spain

    Marta Alonso-Varela, Helena Gil-Peña, Eliecer Coto, Julián Rodríguez, Enrique Rodríguez-Rubio & Fernando Santos

  2. AGC de Pediatría, Hospital Universitario Central de Asturias, 33011, Oviedo, Spain

    Helena Gil-Peña, Julián Rodríguez & Fernando Santos

  3. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

    Helena Gil-Peña, Eliecer Coto, Juan Gómez, Julián Rodríguez & Fernando Santos

  4. AGC Laboratorio – Genética, Hospital Universitario Central de Asturias, Oviedo, Spain

    Eliecer Coto & Juan Gómez

Authors
  1. Marta Alonso-Varela
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  2. Helena Gil-Peña
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  3. Eliecer Coto
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  4. Juan Gómez
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  5. Julián Rodríguez
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  6. Enrique Rodríguez-Rubio
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  7. Fernando Santos
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Consortia

RenalTube Group

  • Ainhoa Iceta
  • , Juan A. Piñero
  • , Gema Ariceta
  • , Sara Chocron
  • , Virginia Cantos
  • , Natalia Mejía
  • , Neus Roca
  • , Ana Peña
  • , Cristina Aparicio
  • , Rosa D. López
  • , Inmaculada Nadal
  • , Susana Ferrando
  • , Raquel López
  • , Fiona Blanco
  • , Luz E. González
  • , Inés Vergara
  • , Alejandro Cruz
  •  & Gloria M. Fraga

Corresponding author

Correspondence to Helena Gil-Peña.

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Alonso-Varela, M., Gil-Peña, H., Coto, E. et al. Distal renal tubular acidosis. Clinical manifestations in patients with different underlying gene mutations. Pediatr Nephrol 33, 1523–1529 (2018). https://doi.org/10.1007/s00467-018-3965-8

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