Autosomal Dominant Hypocalcemia Type 1

Abstract

Gain-of-function mutations of the calcium-sensing receptor (CaSR) lead to disordered mineral homeostasis with disproportionate calcium excretion associated with small increases in blood calcium. Patients with this form of hypoparathyroidism have intractable hypercalciuria leading to nephrocalcinosis and renal damage which may appear, in the more severe cases, during early childhood. This case of severe hypoparathyroidism in a child with a sporadic activating mutation in the CaSR illustrates the overall benefit of parathyroid hormone replacement therapy in managing children with this disorder. Despite early diagnosis during the neonatal period, control of mineral homeostasis was never achieved in infancy and early childhood. This case report describes our 10-year experience treating a child who was referred to us at age 6 years old because of failure to thrive and worsening renal function while receiving conventional therapy with calcitriol, calcium, and thiazide diuretics. Synthetic human parathyroid hormone PTH(1–34) therapy improved her clinical status but reducing urine calcium to normal levels remained a challenge. In an effort achieve normal mineral homeostasis, she was placed first on twice daily then thrice daily injections and finally received PTH delivered by pump which led to the normalization of both serum and urine calcium excretion.