Till Örebro universitet

INTRODUCTION: Vitamin D-dependent rickets type 2A (VDDR2A) is a rare, autosomal recessive disorder caused by pathogenic variants of the VDR gene encoding the vitamin D receptor. It has been proposed to be a form of parathyroid hormone (PTH)-dependent rickets. Here, we describe in detail a girl with VDDR2A who developed a long-standing, tertiary hyperparathyroidism that did not prevent healing of the rickets nor normalization of hypophosphatemia.

CASE PRESENTATION: A girl who presented with seizures at 9 months of age was diagnosed with VDDR2A. She had poor growth, alopecia, severe hypocalcemia, hypophosphatemia, elevated levels of alkaline phosphatase (ALP), PTH and 1,25-dihydroxyvitamin D, and severe rickets. Genetic studies revealed a novel homozygous microdeletion that included exon 9 of the VDR gene. She responded only partially to high oral doses of calcium, cholecalciferol, and alfacalcidol. Upon the initiation of IV calcium infusions, bone pain resolved, and the rickets healed within weeks. In parallel with decreasing ALP values, her phosphate levels normalized even though her PTH levels remained markedly elevated. PTH levels remained elevated for approximately 1 year after the normalization of S-Ca2+. Calcium infusions, despite rendering her mildly hypercalcemic, mostly failed to suppress her PTH into the normal range, consistent with tertiary hyperparathyroidism. The hyperparathyroidism eventually resolved spontaneously with continued high oral doses of calcium, cholecalciferol, and alfacalcidol, which promoted sustained normocalcemia without the need for either cinacalcet or surgery.

CONCLUSION: Persistent tertiary hyperparathyroidism can develop in children with VDDR2A, but does not seem to prevent the healing of rickets nor normalization of hypophosphatemia. High doses of calcium, preferably administered intravenously, seem to be sufficient for the healing of rickets. We speculate that IV calcium compared to oral calcium increases intestinal phosphorus uptake, and once rickets has healed, improved appetite and dietary phosphorus intake together with reduced phosphorus demands due to saturated bones contribute to the normalization of phosphate levels despite persistent hyperparathyroidism.