Neonatal Hypocalcemic Seizures in Offspring of a Mother With Familial Hypocalciuric Hypercalcemia Type 1 (FHH1)

摘要: CONTEXT Familial hypocalciuric hypercalcemia type 1 (FHH1) is caused by loss-of-function mutations of the calcium-sensing receptor (CaSR) and considered a benign condition associated with mild-to-moderate hypercalcemia. However, children parents FHH1 can develop variety disorders calcium homeostasis in infancy. OBJECTIVE The objective this work to characterize range calcitropic phenotypes mother FHH1. METHODS A 3-generation FHH kindred was assessed clinical, biochemical, mutational analysis following informed consent. RESULTS comprised hypercalcemic man his daughter who had hypocalciuria, her 4 children, 2 whom asymptomatic hypercalcemia, normocalcemic, suffered from transient neonatal hypocalcemia seizures. hypocalcemic infant serum 1.57 mmol/L (6.28 mg/dL); normal, 2.0 2.8 (8.0-11.2 mg/dL) parathyroid hormone 2.2 pmol/L; normal 1.0 9.3 pmol/L, required treatment intravenous gluconate infusions. novel heterozygous p.Ser448Pro CaSR variant identified individuals, but not or normocalcemia. Three-dimensional modeling predicted disrupt hydrogen bond interaction within extracellular domain. Pro448 CaSR, when expressed HEK293 cells, significantly impaired CaSR-mediated intracellular mobilization mitogen-activated protein kinase responses stimulation calcium, thereby demonstrating it represent mutation. CONCLUSIONS Thus, hypocalcemia, depending on underlying inherited mutation, require investigations for early childhood.