Novel homozygous inactivating mutation of the calcium-sensing receptor gene (CASR) in neonatal severe hyperparathyroidism-lack of effect of cinacalcet.
Bone
; 64: 102-7, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24735972
ABSTRACT
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 ANDRESULTS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores Sensibles al Calcio
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Homocigoto
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Hiperparatiroidismo
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Enfermedades del Recién Nacido
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Mutación
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Naftalenos
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
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Newborn
Idioma:
En
Revista:
Bone
Asunto de la revista:
METABOLISMO
/
ORTOPEDIA
Año:
2014
Tipo del documento:
Article