title: Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes.
abstract: Autosomal dominant familial hypocalciuric hypercalcemia was found in a kindred with neonatal severe primary hyperparathyroidism, previously judged to be an autosomal recessive trait. Mild hypercalcemia was documented in eight members representing three generations. Mild hypercalcemia was documented at an age as early as one week. In seven adults presumed to be heterozygotes, urinary calcium levels were in the same range as for familial hypocalciuric hypercalcemia. An additional adult member (who previously underwent parathyroidectomy for neonatal severe primary hyperparathyroidism) showed an abnormality in renal clearance of calcium and sodium characteristic of combined familial hypocalciuric hypercalcemia and surgical hypoparathyroidism. Parathyroidectomy in three hypercalcemic members did not cause normocalcemia. Unlike other kindreds with familial hypocalciuric hypercalcemia in whom hypercalcemia is consistent over time and moderate in heterozygotes, this kindred was characterized by heterozygotes showing hypercalcemia that was intermittent and mild. The consanguineous parents of the two previously described severely affected neonates were judged to be heterozygotes for familial hypocalciuric hypercalcemia. In conclusion, (1) a gene presenting as familial hypocalciuric hypercalcemia can be expressed as hypercalcemia that is intermittent and very mild in heterozygotes; (2) such a gene can cause neonatal severe primary hyperparathyroidism in homozygotes.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood* / Q000652:urine*; D005260:Female; D006580:Genetic Carrier Screening; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000235:genetics*; D006961:Hyperparathyroidism / Q000150:complications; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000601:surgery
chemical_list: D002118:Calcium