Atypical skeletal manifestations of rickets in a familial hypocalciuric hypercalcemia patient

Abstract

Familial hypocalciuric hypercalcemia (FHH) is caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene. The loss of function of CaSR 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 CaSR gene revealed a new missense mutation (c.2279T>A) in exon 7, leading to the damaging amino change (p.I760N) in the mature CaSR 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 CaSR mutations may have a partial role in the pathogenesis of skeletal deformities.

Calcium metabolism: Rickets a rare symptom of genetic disease

A report of rickets in a teenage boy has shown that the condition can be a symptom of a genetic disorder that causes calcium imbalances. Familial hypocalciuric hypercalcemia (FHH) is caused by a mutation in the calcium-sensing receptor gene (CASR) and leads to high blood calcium levels and low urine levels. Patients are usually asymptomatic, but mice with the mutation develop skeletal problems. Here, Weibo Xia and colleagues at the Peking Union Medical College Hospital, China, describe the case of a 16-year-old boy who presented with rickets. He was subsequently diagnosed with FHH because he was found to have a previously unseen mutation in the CASR gene. The patient’s clinical profile led the authors to conclude that rickets might be a rare symptom of FHH in patients who also have a mild vitamin D deficiency.

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