【摘要】：Familial hypocalciuric hypercalcemia(FHH) is caused by inactivating mutations in the calcium-sensing receptor(Ca SR) gene. The loss of function of Ca SR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographically. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone(PTH), 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient's Ca SR gene revealed a new missense mutation(c.2279 T4 A) in exon 7, leading to the damaging amino change(p.I760 N) in the mature Ca SR protein, confirming the diagnosis of FHH. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated PTH levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that Ca SR mutations may have a partial role in the pathogenesis of skeletal deformities.
[Abstract]:Familial hypocalciuric hypercalcemia(FHH) is caused by inactivating mutations in the calcium-sensing receptor(Ca SR) gene. The loss of function of Ca SR presents with rickets as the predominant skeletal abnormality in mice, but is rarely reported in humans. Here we report a case of a 16-year-old boy with FHH who presented with skeletal manifestations of rickets. To identify the possible pathogenic mutation, the patient was evaluated clinically, biochemically, and radiographically. The patient and his family members were screened for genetic mutations. Physical examination revealed a pigeon breast deformity and X-ray examinations showed epiphyseal broadening, both of which indicate rickets. Biochemical tests also showed increased parathyroid hormone(PTH), 1,25-dihydroxyvitamin D, and elevated ionized calcium. Based on these results, a diagnosis of FHH was suspected. Sequence analysis of the patient's Ca SR gene revealed a new missense mutation(c.2279 T4 A) in exon 7, leading to the damaging amino change(p.I760 N) in the mature Ca SR protein, confirming the diagnosis of FHH. Moreover, the skeletal abnormities may be related to but not limited to vitamin D abnormity. Elevated PTH levels and a rapid skeletal growth period in adolescence may have also contributed. Our study revealed that rickets-like features have a tendency to present atypically in FHH patients who have a mild vitamin D deficiency, and that Ca SR mutations may have a partial role in the pathogenesis of skeletal deformities.
【作者單位】： Department
【基金】：supported by the National Natural Science Foundation of China(nos.81070687 and 81170805) Beijing Natural Science Foundation(no.7121012) Ministry of Science and Technology of the People’s Republic of China(National Science and Technology Major Projects for‘Major New Drugs Innovation and Development 2008ZX09312-016) Scientific Research Foundation of Beijing Medical Development(no.2007-3029) National Key Program of Clinical Science(WBYZ2011-873)
【分類號】：R589

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