Autosomal Dominant Hypocalcemia With Hypercalciuria Due to a Calcium-Sensing Receptor Gain-of-Function Mutation: A...

Autosomal dominant hypocalcemia with hypercalciuria (ADHH) is a rare genetic disorder caused by gain-of-function mutations in the calcium-sensing receptor (CaSR) gene. It is characterized by hypocalcemia, inappropriately low parathyroid hormone (PTH), and renal hypercalciuria. We describe a 13-year-old boy who was diagnosed with congenital hypoparathyroidism, persistent hypercalciuria, and mild medullary nephrocalcinosis. Despite calcium and vitamin D supplementation, hypercalciuria was aggravated. Genetic testing revealed a heterozygous c.2518G>A (p.Gly840Ser) mutation in the CaSR gene, classified as likely pathogenic (American College of Medical Genetics and Genomics (ACMG) Class 4). Supplementation was discontinued, and hydrochlorothiazide and potassium citrate were initiated to reduce urinary calcium and alkalinize urine. At the one-year follow-up, renal function remained preserved with no progression of nephrocalcinosis. This case underscores the importance of considering ADHH in children with hypocalcemia, suppressed PTH, and renal hypercalciuria. Early genetic testing prevents misdiagnosis and enables targeted therapy to mitigate long-term renal complications.