Marguerite Hureaux1,2,3, Arnaud Molin4,5,6, Nadine Jay7, Anne Hélène Saliou8, Emmanuel Spaggiari9, Rémi Salomon2,3,10, Alexandra Benachi11, Rosa Vargas-Poussou12,13, Laurence Heidet3,10. 1. Département de Génétique, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20-40 rue Leblanc, 75015, Paris, France. 2. Paris Descartes-Sorbonne Paris Cité University, Paris, France. 3. Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Filière ORKiD, Paris, France. 4. Service de Génétique, Centre Hospitalier Universitaire de Caen, Caen, France. 5. Centre de Référence des Maladies rares du Métabolisme du calcium et du phosphate (filière OSCAR), FilièreOSCAR, Paris, France. 6. Université Caen Normandie, UFR de médecine (Medical School), EA7450 BioTarGen, Caen, France. 7. Centre Hospitalier Universitaire de Brest, Service de Pédiatrie et Génétique Médicale, Brest, France. 8. Centre Pluridisciplinaire de Diagnostic Prénatal, CHRU, Brest, France. 9. Département de Gynécologie-Obstétrique, Assistance Publique Hôpitaux de Paris, Hôpital Necker - Enfants Malades, Paris, France. 10. Département de Néphrologie Pédiatrique, Assistance Publique Hôpitaux de Paris, Hôpital Necker - Enfants Malades, Paris, France. 11. Département de Gynécologie-Obstétrique, Assistance Publique Hôpitaux de Paris, Hôpital Antoine-Béclère, Université Paris-Sud, Clamart, France. 12. Département de Génétique, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20-40 rue Leblanc, 75015, Paris, France. rosa.vargas@aphp.fr. 13. Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Filière ORKiD, Paris, France. rosa.vargas@aphp.fr.
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.
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 phosphatemetabolism 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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