Association of parathyroid adenoma and familial hypocalciuric hypercalcaemia in a teenager.
OBJECTIVE
Familial hypocalciuric hypercalcaemia (FHH) is clinically characterized by mild to moderate parathyroid hormone (PTH)-dependent hypercalcaemia, autosomal dominant pattern of inheritance, and normal to frankly reduced urinary calcium excretion in spite of a high serum calcium (clearance (Ca)/clearance (Cr)<0.01). FHH has a benign course and should be differentiated from primary hyperparathyroidism. It is usually caused by a heterozygous loss-of-function mutation in the calcium-sensing receptor gene (CASR).


METHODS
We report the case of a 16-year-old patient with hypercalcaemia and a mixed family history of parathyroid adenoma and mild hypercalcaemia. Serum calcium was 14 mg/dl with a serum iPTH of 253 pg/ml.


RESULTS
A neck 99mTc-sesta MIBI tomoscintigraphy showed a definite hyperactivity in the left upper quadrant. A surgical four-gland exploration confirmed a single parathyroid adenoma. After surgical resection of a left superior parathyroid adenoma, the patient's hypercalcemia improved but did not normalize, returning to a level typical of FHH. An inactivating mutation in exon 4 of the CASR gene, predicting a p.Glu297Lys amino acid substitution was found.


CONCLUSIONS
Thus, this 16-year old patient presented with the association of FHH and a single parathyroid adenoma. The young age of the patient and the association of parathyroid adenoma and FHH in his grandmother argue for a causal link between CASR mutation and parathyroid adenoma in this family. This case contributes to illustrate the expanding clinical spectrum of CASR loss-of-function mutations.
Pediatrics, Hôpital Universitaire des Enfants Reine Fabiola, U.L.B., 15, Avenue J.J. Crocq, 1020 Brussels, Belgium. cecile.brachet@huderf.be
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C
Brachet
E
E
Boros
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Tenoutasse
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Lissens
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G
Andry
P
P
Martin
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P
Bergmann
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C
Heinrichs
D000236:Adenoma / Q000150:complications / Q000235:genetics*; D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D002118:Calcium / Q000097:blood / Q000652:urine; D005091:Exons / Q000235:genetics; D005192:Family Health; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000235:genetics*; D008297:Male; D010282:Parathyroid Neoplasms / Q000150:complications / Q000235:genetics*; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
C095550:CASR protein, human; D044169:Receptors, Calcium-Sensing; D002118:Calcium