FAMILIAL ISOLATED PRIMARY HYPERPARATHYROIDISM

Familial primary hyperparathyroidism (PHPT) is usually encountered in the context of multiple endocrine neoplasia (MEN) syndromes. Few famil ies have been reported in the literature where PHPT was the only abnor mality. However, in these families no long-term follow-up data were re ported and no genetic linkage studies were performed. OBJECTIVE We inv estigated a large family with a familiar primary hyperparathyroidism f or biochemical and genetic markers of multiple endocrine neoplasia syn dromes. DESIGN A family screening study. PATIENTS Thirty-seven family members participated in this study including 7 patients who had been p reviously operated upon for PHPT. MEASUREMENTS Serum calcium (albumin adjusted), was measured in all family members. Hypercalcaemic subjects and patients who had been operated upon for PHPT were assessed for bi ochemical markers of MEN syndromes (serum gastrin, prolactin, calciton in, fasting plasma glucose and 24-hours urinary excretion of adrenalin e, noradrenaline and vanillylmandelic acid (VMA)). Genetic linkage ana lysis was performed using DNA markers linked to chromosome 11q13, the presumed MEN type 1 (MEN-1) locus. RESULTS Four new patients with PHPT and two with probable PHPT were discovered. No clinical or biochemica l evidence of MEN syndromes could be detected. DNA marker pMS51(D11S97 ) was informative, maximum two-point lodscore of 2.12 at a recombinati on fraction of 0.05 confirming linkage to chromosome 11q13. CONCLUSION S Familial PHPT can exist as a separate clinical entity. Isolated fami liar PHPT is caused by mutation in a gene located in the MEN-1 region on chromosome 11q13, possibly the MEN-1 locus.