TRPV6-related intrauterine calciopenic rickets: a case report and literature review

Summary: We report a female Chinese neonate with antenatal rickets and secondary hyperparathyroidism who was found to have novel compound heterozygous TRPV6 variants (c.1160G>A and c.658C>T). She was treated with calcium, phosphate and vitamin D supplementation, achieving full biochemical and radiographic recovery by age two years. The review of all 14 reported cases confirms a consistent phenotype of neonatal secondary hyperparathyroidism with universal parathyroid hormone (PTH) elevation, frequent fractures and respiratory distress. Excellent outcomes are achieved with supplementation. The correlation between vitamin D deficiency and hypocalcaemia in these neonates suggests that maternal vitamin D status may modify disease severity. Learning points: TRPV6 mutations should be considered a rare cause of neonatal prenatal rickets and secondary hyperparathyroidism, even in the presence of normocalcaemic hyperparathyroidism. Prognosis is excellent with early mineral and vitamin D supplementation. Multidisciplinary care is essential for diagnosis, management and follow-up. Maternal vitamin D status may modulate disease severity, suggesting that prenatal supplementation could be beneficial.