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Prenatal hyperechogenic kidneys in three cases of infantile hypercalcemia associated with SLC34A1 mutations

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Abstract

Background

Prenatal diagnosis of hyperechogenic kidneys is associated with a wide range of etiologies and prognoses. The recent advances in fetal ultrasound associated with the development of next-generation sequencing for molecular analysis have enlarged the spectrum of etiologies, making antenatal diagnosis a very challenging discipline. Of the various known causes of hyperechogenic fetal kidneys, calcium and phosphate metabolism disorders represent a rare cause. An accurate diagnosis is crucial for providing appropriate genetic counseling and medical follow-up after birth.

Methods

We report on three cases of fetal hyperechogenic kidneys corresponding to postnatal diagnosis of nephrocalcinosis. In all cases, antenatal ultrasound showed hyperechogenic kidneys of normal to large size from 22 gestational weeks, with a normal amount of amniotic fluid. Postnatal ultrasound follow-up showed nephrocalcinosis associated with hypercalcemia, hypercalciuria, elevated 1,25(OH)2-vitamin D, and suppressed parathyroid hormone levels.

Results

Molecular genetic analysis by next-generation sequencing performed after birth in the three newborns revealed biallelic pathogenic variants in the SLC34A1 gene, encoding the sodium/phosphate cotransporter type 2 (Npt2a), confirming the diagnosis of infantile hypercalcemia.

Conclusions

Nephrocalcinosis due to infantile hypercalcemia can be a cause of fetal hyperechogenic kidneys, which suggests early antenatal anomaly of calcium and phosphate metabolism. This entity should be considered in differential diagnosis. Postnatal follow-up of infants with hyperechogenic kidneys should include evaluation of calcium and phosphate metabolism.

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Funding

Funding for this study was in part provided by the European Union, FP7 (grant agreement 2012-305608) “European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics).”

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Authors and Affiliations

  1. Département de Génétique, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20-40 rue Leblanc, 75015, Paris, France

    Marguerite Hureaux & Rosa Vargas-Poussou

  2. Paris Descartes-Sorbonne Paris Cité University, Paris, France

    Marguerite Hureaux & Rémi Salomon

  3. Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte (MARHEA), Filière ORKiD, Paris, France

    Marguerite Hureaux, Rémi Salomon, Rosa Vargas-Poussou & Laurence Heidet

  4. Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, France

    Arnaud Molin

  5. Centre de Référence des Maladies rares du Métabolisme du calcium et du phosphate (filière OSCAR), FilièreOSCAR, Paris, France

    Arnaud Molin

  6. Université Caen Normandie, UFR de médecine (Medical School), EA7450 BioTarGen, Caen, France

    Arnaud Molin

  7. Centre Hospitalier Universitaire de Brest, Service de Pédiatrie et Génétique Médicale, Brest, France

    Nadine Jay

  8. Centre Pluridisciplinaire de Diagnostic Prénatal, CHRU, Brest, France

    Anne Hélène Saliou

  9. Département de Gynécologie-Obstétrique, Assistance Publique Hôpitaux de Paris, Hôpital Necker – Enfants Malades, Paris, France

    Emmanuel Spaggiari

  10. Département de Néphrologie Pédiatrique, Assistance Publique Hôpitaux de Paris, Hôpital Necker – Enfants Malades, Paris, France

    Rémi Salomon & Laurence Heidet

  11. Département de Gynécologie-Obstétrique, Assistance Publique Hôpitaux de Paris, Hôpital Antoine-Béclère, Université Paris-Sud, Clamart, France

    Alexandra Benachi

Authors
  1. Marguerite Hureaux
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  2. Arnaud Molin
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  3. Nadine Jay
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  4. Anne Hélène Saliou
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  5. Emmanuel Spaggiari
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  6. Rémi Salomon
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  7. Alexandra Benachi
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  8. Rosa Vargas-Poussou
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  9. Laurence Heidet
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Corresponding author

Correspondence to Rosa Vargas-Poussou.

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Hureaux, M., Molin, A., Jay, N. et al. Prenatal hyperechogenic kidneys in three cases of infantile hypercalcemia associated with SLC34A1 mutations. Pediatr Nephrol 33, 1723–1729 (2018). https://doi.org/10.1007/s00467-018-3998-z

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  • DOI: https://doi.org/10.1007/s00467-018-3998-z

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