Casting new light on the clinical spectrum of neonatal severe hyperparathyroidism

Functional Deletion of the Calcium-Sensing Receptor in a Case of Neonatal Severe Hyperparathyroidism

“…Skeletal radiographs clearly demonstrated effects of hyperparathyroidism, including undermineralization of bone, particularly at the extremities. Surprisingly, however, there was no evidence of fractures, a common finding in NSHPT (9,13). In addition, some of the skeletal deformities observed in the knockout mouse and/or NSHPT (9,18), such as bowing of the long bones and deficiencies in the extension of the digits, were not evident in this case.…”

“…The clinical features, biochemical parameters, and x-rays exhibiting changes of hyperparathyroidism in this case were highly suggestive of NSHPT (13). These findings, together with the fact that the infant's maternal relatives were already being investigated for presumed FHH, prompted us to perform heterozygous sequence analysis of his CaR DNA.…”

“…On the other hand, parathyroids from NSHPT patients show a markedly higher set-point for calcium responsiveness, and this condition is associated with parathyroid gland hyperplasia, severe hypercalcemia, and elevated circulating PTH levels accompanied by symptoms in the neonate, which include failure to thrive, dehydration, respiratory distress, hypotonia, skeletal undermineralization, and significant mortality. Urgent surgical intervention in the form of parathyroidectomy and appropriate follow-up treatment is normally required to correct the condition (13). We show here a case of NSHPT involving compound heterozygous mutations of the CaR that led to an effective knockout of functional receptor.…”

Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review

“…67 However, this disease has variable expression and on investigation of the family it is not unusual to ¢nd that only one parent (usually the father) has FBHH. 61 There are also cases in which neither parent has FBHH but the de novo mutation is su⁄ciently severe and dominant to produce the symptoms, e.g. the R185Q mutation.…”

Calcimimétiques et traitement des hyper-parathyroïdies

“…Pour la première fois, il a été démontré qu'un récep-teur protéique pouvait fixer et être activé par une molécule inorganique, en l'occurrence le calcium. Ce clonage a permis de connaître sa structure protéique et ses voies de signalisation intracellulaire, le diagnostic précis de plusieurs maladies congénitales et acquises dues à des mutations dans le gène codant pour le CaR [2,3], et le développe-ment des molécules pouvant moduler l'activité du CaR, notamment les calcimimétiques et les calcilytiques (Figure 1) (➜). Les calcimimétiques sont des molécules capables de rendre le CaR plus sensible aux effets du Ca 2+ ec .…”