FHH is typically a benign condition. Little is known about its course and management during pregnancy. Two sisters with presumed FHH were followed prospectively through their pregnancies for clinical course and biochemical parameters. Their kindred were retrospectively examined across four generations for available information. Genetic testing for inactivating mutations of the calcium sensing receptor (CaSR) was performed in two women and in other members where possible.
The index case demonstrated incidental hypercalcaemia (corrected calcium 3.03mM), low normal PTH (1.3pM), 25-hydroxyvitamin D insufficiency (34nM) and fractional calcium excretion of 1.7% during pregnancy. Her pregnant sister also had incidental hypercalcaemia (corrected calcium 2.9mM), normal phosphate (0.86mM), low normal PTH (3.1pM), 25-OH vitamin D insufficiency (34nM) and fractional calcium excretion of 0.9%. Both were heterozygous for the R220W missense mutation of the CaSR in addition to the R990G and A986S polymorphisms. A third pregnant member of the kindred had persistent hypercalcaemia despite previous parathyroidectomy. Biochemistry at 36 weeks gestation showed corrected calcium of 2.61mM, PTH of 2.3pM and 25-OH vitamin D of 53nM. All three had uncomplicated, term pregnancies without neonatal complications.
Asymptomatic hypercalcaemia was the typical presentation in this kindred. Corrected calcium levels ranged between 2.86 – 3.02 mM and PTH levels ranged from low to high normal (3.1 – 10.6 pM). Fractional excretion of calcium in this kindred ranged from 0.6 – 1.7%. Three members had previously undergone parathyroidectomy and two exhibited persistent post-operative hypercalcaemia.
FHH was described in this kindred based on the inheritance patterns, clinical courses and biochemical parameters, and confirmed on genetic testing. Our prospective observation suggests that FHH runs a benign course in pregnancy. The tools available for the diagnosis of FHH include urinary calcium excretion and gene testing. It is important to differentiate FHH from primary hyperparathyroidism to prevent unnecessary parathyroid surgery. Variations in the inherited mutations of the calcium sensing receptor may explain the diversity of serum calcium levels and specific clinical phenotypes.