Chapter 57 - Familial Benign Hypocalciuric Hypercalcemia and Neonatal Primary Hyperparathyroidism

Abstract

This chapter discusses familial benign hypocalciuric hypercalcemia (FBHH) and Neonatal Primary Hyperparathyroidism. The FBHH syndrome is inherited in an autosomal dominant fashion and is usually characterized by lifelong asymptomatic hypercalcemia, relative hypocalciuria, and the lack of the classical complications of hypercalcemia, including bone disease and renal stone disease. Some observers have also suggested that FBHH increases the risk of acute pancreatitis. The skeleton in patients with FBHH generally appears to be normal histologically, radiographically, and by mineral densitometry. While FBHH does not appear to threaten skeletal integrity, it does not confer immunity to osteoporosis. The relatively low urinary excretion of calcium in FBHH results from avid renal tubular reabsorption of calcium, and the urinary excretion of magnesium is unexpectedly low given that the serum level is in the upper part of the normal range or, in some cases, mildly elevated. Studies of the FBHH syndrome have almost uniformly suggested a genetic disorder of calcium sensing by the parathyroid gland paired with enhanced renal tubular reabsorption of calcium. PTH secretion persists at normal or slightly elevated values in the face of hypercalcemia, but without obvious disturbances of other calcium-regulating hormone concentrations. These pathophysiologic abnormalities would be most parsimoniously explained by dominant mutations of a single calcium sensing receptor expressed both in parathyroid glands and in kidneys. Neonatal primary hyperparathyroidism can be a mild syndrome representing the neonatal expression of FBHH, or it can present as a much more dramatic disease with high morbidity and even mortality if untreated, which is known as neonatal severe primary hyperparathyroidism (NSHPT).