Enamel renal syndrome due to FAM20A mutations: challenging kidney management in view of nephrocalcinosis, hypophosphatemia and hypocalciuria.

backgroundEnamel Renal Syndrome (ERS) is a rare disorder characterized by a combination of dental and renal abnormalities, including stones and hypophosphatemia. ERS is genetically heterogeneous.

methodsWe report on four pediatric cases of homozygous LoF FAM20A mutations (2 families). Biological (including oral calcium load) and imaging (dental and renal) data were reviewed. Results are presented as median(range).

resultsAll patients were referred for renal screening by the specialized dental team at a median age of 14.5 [11–19] years. None of them presented symptoms of microscopic/macroscopic hematuria, nor renal colic despite the presence of multiple bilateral nephrolithiasis in all and nephrocalcinosis in one family. Biological parameters were vastly similar, with preserved renal function (eGFR 109(93–111) mL/min/1.73 m²), hypophosphatemia (median − 1.9(-3.4;-1.7) SDS for age), elevated FGF-23 (98(84–117) RU/mL, normal range 21–91 RU/mL) with hypocalciuria and low TmP/GFR. Oral calcium load tests confirmed the absence of resorptive and absorptive hypercalciuria, with adequate PTH inhibition during the test; of note, “baseline” PTH levels tended to be at the upper normal limit (83(65–131) ng/L, local upper normal limit 65ng/L) that was not adequate in view of hypophosphatemia, with 25D levels at 44(19–92) nmol/L. All patients were subsequently followed in pediatric nephrology and received hyperhydration and prudent vitamin D supplementation.

conclusionThese cases highlight the need for interdisciplinary collaboration between pediatric nephrologists, dental specialists and geneticists, to ensure that patients receive timely renal evaluation. The identification of elevated FGF-23 levels in FAM20A-related ERS with severe nephrolithiasis and hypophosphatemia raises the question of the interest of burosumab as targeted therapy.