A genetic disorder that is characterized by decreased urinary calcium excretion and (usually asymptomatic) hypercalcemia. PTH levels are normal in most patients. Caused by an autosomal dominant mutation of a calcium-sensing receptor in the kidneys and parathyroid gland (CaSR gene).

  • Clinical features
    • Usually asymptomatic
    • Neonatal hypocalcemia in children of mothers with FHH (e.g., paresthesias, muscle spasms, seizures)
  • Diagnosis
    • Key Labs:
      • Mildly elevated serum Ca (usually < 12 mg/dL).
      • Normal to mildly elevated PTH (inappropriate in the setting of hypercalcemia).
      • Low 24-hour urine Ca excretion (< 100 mg/24h).
    • Confirmatory/Gold Standard:
      • Urine Calcium-to-Creatinine Clearance Ratio (UCCR)< 0.01 (UCCR = [Urine Ca × Serum Cr] / [Serum Ca × Urine Cr]). c
      • Genetic testing for CASR gene mutations (used if UCCR is borderline between 0.01 and 0.02).
  • Differential diagnostics
    • Primary Hyperparathyroidism (PHPT):
      • Diff by: UCCR > 0.02, high 24-hour urine Ca (> 200 mg/24h), and complications like nephrolithiasis or osteoporosis. c
    • Humoral Hypercalcemia of Malignancy:
      • Diff by: High serum Ca, suppressed PTH, elevated PTHrP, and severe systemic symptoms.
    • Lithium-induced Hypercalcemia:
      • Diff by: History of lithium use; mimics FHH by raising the set-point of CaSR.
  • Therapy
    • No treatment necessary