Familial hypocalciuric hypercalcaemia: a study of four kindreds

Abstract

Four kindreds with hereditary hypercalcaemia have been investigated. Thirty-seven of 72 subjects examined had hypercalcaemia with an autosomal dominant pattern of inheritance. Hypercalcaemic patients had total serum calcium of 2.91 +/- 0.12 mmol l-1. Serum parathyroid hormone (PTH) was normal while daily urinary calcium excretion was subnormal (below 2.5 mmol) in 45%. Comparison with an age-matched group of patients with primary hyperparathyroidism gave a small overlap regarding serum human PTH, urinary calcium and the ratio between calcium clearance and creatinine clearance. Family screening therefore is of diagnostic importance. Twelve subjects had been subjected to parathyroid surgery before the correct diagnosis was settled, none of the cases had an adenoma. Three patients became normocalcaemic and the others had persistent hypercalcaemia. One male non-abuser had seven episodes of acute pancreatitis before surgery and none after. The findings in all four kindreds are compatible with familial hypocalciuric hypercalcaemia (FHH). This hereditary disorder of unknown aetiology, therefore, also exists in Scandinavia. It is of importance to consider FHH in the differential diagnosis of hypercalcaemia, since this disorder usually has a benign prognosis if untreated.

Clinical and laboratory features of calcium-sensing receptor disorders: a systematic review

“…The extra measured parameter, serum calcium, rarely exceeds 3.2 mmol/L in FBHH. 1,6,7,9,12,13,18,29,43 In two early extensive reviews, 3,15 occasional values up to 3.5 mmol/L were reported. Therefore, serum calcium may have higher values in PHPT than in FBHH 6,7 and result in a lower calcium:creatinine clearance ratio in some cases, and thus a greater overlap in results.…”

“…The numbers of subjects from each study, with the range and median of the six most commonly studied biochemical parameters overall, are summarized in Table 3. Of the 10 studies, three were of a single large kindred, 1,13,18 ¢ve consisted of series of cases of FBHH and PHPT collected separately over unspeci¢ed time periods, 3,9,12,42,43 and two were prospective studies of unselected cases of hypercalcaemia over a 3-year period in the same hospital. 6,7 A spreadsheet containing the original data from these studies is available at www.acb.org.uk/annclinbiochem/ webwise/ADHHClinBiochem.xls and www.acb.org.uk/ annclinbiochem/webwise/FBHHCalciumdata.xls Table 4 summarizes data for the six most commonly measured biochemical parameters.…”

Familial Hypocalciuric Hypercalcemia in Israel: A Preliminary Report

“…Marx et al [2] identified familial hypercalcemia in 13 out of 25 patients (52%) with parathyroid hyperplasia; but only 2 patients out of the 13 (13%) with familial hypercalcemia Sporadic reports of FHH kindreds appeared from France [20][21][22], Spain [23], Norway [24], Sweden [25], Denmark [26,27], the Netherlands [16,28], Italy [29], Switzerland [30], and Japan [31][32][33][34]. This limited data suggests that FHH is prevalent in many parts of the world, but no specific conclusions can be drawn about its ethnic distribution.…”

Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism

“…It is characterized by asymptomatic and usually uncomplicated lifelong hypercalcemia. [1][2][3][31][32][33][34]37,38 It was estimated that FHH accounted for about 9% of failed parathyroidectomies in patients presenting to the NIH in the 1970s, 39 the proportion was 23% in a more recent series from Denmark. Longevity is normal as demonstrated in large studies from the National Institutes of Health, the Mayo Clinic, and others.…”

“…43,44 Furthermore, there appears to be no increased incidence of fractures in FHH, and the skeletons of these patients are normal by histomorphometric, radiologic, and densitometry criteria. [31][32][33][34]37,38,43,[45][46][47] Unfortunately, FHH does not provide immunity against age-related bone loss; elderly patients with FHH may have osteoporosis indistinguishable from that expected for their age.…”