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

International Journal of Pediatric Endocrinology

Nancy S Dunbar²  Stephen O’Connor¹  Ksenia N Tonyushkina² 

[1] Baystate Medical Center, Tufts University School of Medicine, 759 Chestnut St. Dept of Radiology, Springfield, MA 01199, USA;Baystate Children’s Hospital, Tufts University School of Medicine, 759 Chestnut St. Dept of Pediatrics, Springfield, MA 01199, USA

关键词: Vit D;    CaSR;    NHPT;    Hypercalcemia;    Neonatal hyperparathyroidism;    FHH;   

Others  :  813528
DOI  :  10.1186/1687-9856-2012-13

 received in 2012-02-21, accepted in 2012-05-23,  发布年份 2012

【 摘 要 】

Background

Familial Hypocalciuric Hypercalcemia (FHH) is a generally benign disorder caused by heterozygous inactivating mutations in the Calcium-Sensing Receptor (CaSR) gene resulting in altered calcium metabolism.

Objective

We report a case of unusually severe neonatal FHH due to a novel CaSR gene mutation that presented with perinatal fractures and moderate hypercalcemia.

Case overview

A female infant was admitted at 2 weeks of age for suspected non-accidental trauma (NAT). Laboratory testing revealed hypercalcemia (3.08 mmol/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, 400 IU/day, and by 6 weeks of age, iPTH levels had decreased into the high-normal range. Follow up radiographs demonstrated marked improvement of bone lesions by 3 months. A CaSR gene mutation study showed heterozygosity for a T>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 18 months of age, the child continues to have relative hyperparathyroidism and moderate hypercalcemia but is otherwise normal.

Conclusion

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.

【 授权许可】

   
2012 Tonyushkina et al.; licensee BioMed Central Ltd.

【 图 表 】

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