Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet.

BACKGROUND: NSHPT is a life-threatening disorder caused by homozygous inactivating calcium-sensing receptor (CASR) mutations. In some cases, the CaSR allosteric activator, cinacalcet, may reduce serum PTH and calcium levels, but surgery is the treatment of choice. OBJECTIVE: To describe a case of NSHPT unresponsive to cinacalcet. PATIENT AND RESULTS: A 23-day-old girl was admitted with hypercalcemia, hypotonia, bell-shaped chest and respiratory distress. The parents were first-degree cousins once removed. Serum Ca was 4.75 mmol/l (N: 2.10-2.62), P: 0.83 mmol/l (1.55-2.64), PTH: 1096 pg/ml (9-52) and urinary Ca/Cr ratio: 0.5mg/mg. First, calcitonin was given (10 IU/kg × 4/day), and then 2 days later, pamidronate (0.5mg/kg) for 2 days. Doses of cinacalcet were given daily from day 28 of life starting at 30 mg/m2 and increasing to 90 mg/m2 on day 43. On day 33, 6 days after pamidronate, serum Ca levels had fallen to 2.5 mmol/l but, thereafter, rose to 5 mmol/l despite the cinacalcet. Total parathyroidectomy was performed at day 45. Hungry bone disease after surgery required daily Ca replacement and calcitriol for 18 days. At 3 months, the girl was mildly hypercalcemic, with no supplementation, and at 6 months, she developed hypocalcemia and has since been maintained on Ca and calcitriol. By CASR mutation analysis, the infant was homozygous and both parents heterozygous for a deletion-frameshift mutation. CONCLUSION: The predicted nonfunctional CaSR is consistent with lack of response to cinacalcet, but total parathyroidectomy was successful. An empiric trial of the drug and/or prompt mutation testing should help minimize the period of unnecessary pharmacotherapy.

Quantitative ultrasound and biochemical parameters for the assessment of osteopenia in preterm infants.

OBJECTIVE: Our study aimed to evaluate the feasibility of quantitative ultrasound (QUS) evaluation in osteopenia of prematurity and to compare the results to biochemical parameters. METHODS: QUS assessment of bone was performed at the end of the first postnatal week and at term-corrected age (CA) in premature infants (N = 30) and within the first week in full-term infants (N = 25). On the same day of measurement of QUS, the serum calcium, phosphorus (inorganic), and alkaline phosphatase (ALP) activity were measured in the preterm infants. RESULTS: The median of tibia z score at term-CA in premature infants was significantly lower compared to that of first postnatal week (-1 and 0.4, respectively; p < 0.0001) and it was also lower than that of term-matched controls (0.0; p = 0.001). Preterm infants at term-CA had lower weights and lengths in comparison to term infants. The median ALP value was 585 IU/L at the first postnatal week and 703 IU/L at term-CA in preterm infants (p = 0.003). The median tibia z score of infants with ALP >or=900 IU/L was significantly lower than that of the infants with ALP <900 IU/L (-1.4 vs. 0.1; p = 0.001). An inverse correlation was found between ALP levels and tibia z score at term-CA in preterm infants (rho = -0.61, p = 0.01). CONCLUSIONS: Bone density of preterm infants at term-CA was lower than that at first postnatal week. Serum ALP levels increased during the first postnatal weeks. The tibia z scores were correlated to serum ALP levels. QUS is a good screening tool for the detection of osteopenia.