A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia

作者：Ksenia N Tonyushkina; Stephen O' Connor; Nancy S Dunbar

来源：International Journal of Pediatric Endocrinology, 2012.

DOI：10.1186/1687-9856-2012-13

• FHH
• Neonatal hyperparathyroidism
• Hypercalcemia
• NHPT
• CaSR
• Vit D

We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia.A female infant was admitted at 2ˋweeks of age for suspected non-accidental trauma (NAT). Laboratory testing revealed hypercalcemia (3.08ˋmmol/L), elevated iPTH (20.4 pmol/L) and low urinary calcium clearance (0.0004). Radiographs demonstrated multiple healing metaphyseal and rib fractures and bilateral femoral bowing. The femoral deformity and stage of healing were consistent with prenatal injuries rather than non-accidental trauma (NAT). Treatment was initiated with cholecalciferol, 400ˋIU/day, and by 6ˋweeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3ˋmonths. A CaSR gene mutation study showed heterozygosity for a T%26gt;C nucleotide substitution at c.1664 in exon 6, resulting in amino acid change I555T in the extracellular domain consistent with a missense mutation. Her mother does not carry the mutation and the father is unknown. At 18ˋmonths of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal.This neonate with intrauterine fractures and demineralization, moderate hypercalcemia and hyperparathyroidism was found to have a novel inactivating missense mutation of the CaSR not detected in her mother. Resolution of bone lesions and reduction of hyperparathyroidism was likely attributable to the natural evolution of the disorder in infancy as well as the mitigating effect of cholecalciferol treatment.

• 出版日期2012