Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype.

@article{Pollak1994FamilialHH,
  title={Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Effects of mutant gene dosage on phenotype.},
  author={M. Pollak and Y. Chou and S. Marx and B. Steinmann and D. Cole and M. Brandi and S. Papapoulos and F. Menko and G. Hendy and E. Brown},
  journal={The Journal of clinical investigation},
  year={1994},
  volume={93 3},
  pages={
          1108-12
        }
}
Neonatal severe hyperparathyroidism is a rare life-threatening disorder characterized by very high serum calcium concentrations (> 15 mg/dl). Many cases have occurred in families with familial hypocalciuric hypercalcemia, a benign condition transmitted as a dominant trait. Among several hypothesized relationships between the two syndromes is the suggestion that neonatal severe hyperparathyroidism is the homozygous form of familial hypocalciuric hypercalcemia. To test this hypothesis, we refined… Expand
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In counseling affected families, the heterozygous state should not be considered entirely benign, since FHH heterozygotes, particularly infants, may be prone to secondary hyperparathyroidism and symptomatic hypercalcemia, and molecular diagnosis will allow for unambiguous identification of at-risk individuals. Expand
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Benign familial hypocalciuric hyperCalcemia is a small but important cause of hypercalcemia, especially in the younger population, and affected patients should be advised against surgical intervention. Expand
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In NSHPT, the homozygotes for pathogenic CASR variants show higher calcium and PTH than heterozygotes, which supports early and robust diagnosis of CASR dosage. Expand
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References

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Familial hypocalciuric hypercalcemia. Mild expression of the gene in heterozygotes and severe expression in homozygotes.
TLDR
A gene presenting as familial hypocalciuric hypercalcemia can be expressed as hyperCalcemia that is intermittent and very mild in heterozygotes and such a gene can cause neonatal severe primary hyperparathyroidism in homozygotes. Expand
Neonatal severe primary hyperparathyroidism and alkaptonuria in a boy born to related parents with familial hypocalciuric hypercalcemia.
TLDR
It is speculated that homozygosity for the 'FHH-gene' is the cause of the life-threatening manifestation of NSPHP, whereas heterozygosityfor the same gene leads to FHH, by comparison a mild disorder. Expand
Genetic linkage analysis in familial benign (hypocalciuric) hypercalcemia: evidence for locus heterogeneity.
TLDR
The FBH phenotype results from mutations at two separate loci on chromosomes 3q and 19p, tightly linked to the marker loci D 19S20 and D19S266. Expand
An association between neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia in three kindreds.
TLDR
The association of two uncommon syndromes (neonatal severe primary hyperparathyroidism and familial hypocalciuric hypercalcemia) in these kindreds suggests that the two syndrome share a common genetic cause within each kindred. Expand
The gene responsible for familial hypocalciuric hypercalcemia maps to chromosome 3q in four unrelated families
TLDR
It is suggested that the causal gene is important for maintenance of extracellular calcium homeostasis by the parathyroid gland and kidney and that identification of the FHH gene will improve understanding of the molecular basis for physiologic and pathologic regulation of calcium. Expand
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TLDR
Familial benign hyperCalcemia or hypocalciuric hypercalcemia is a distinctive heritable syndrome that should always be considered in the differential diagnosis of asymptomatic hypercalccemia. Expand
Urinary calcium excretion in familial hypocalciuric hypercalcemia. Persistence of relative hypocalciuria after induction of hypoparathyroidism.
TLDR
The greater calciuric response to ethacrynic acid than to acetazolamide or calcium infusion alone in FHH indicates that a major renal locus of abnormal calcium transport in this disorder may be the ascending limb of the loop of Henle. Expand
Severe primary hyperparathyroidism in a neonate with two hypercalcemic parents: management with parathyroidectomy and heterotopic autotransplantation.
TLDR
A neonate with severe primary hyperparathyroidism was successfully managed by parathyroidectomy and heterotopic autotransplantation, and relative hypocalciuria in the presence of hypercalcemia was found in the mother; in contrast, the father had hypercalciuria. Expand
Family studies in patients with primary parathyroid hyperplasia.
TLDR
Distinction of the two conditions is important since patients with FHH may not benefit from subtotal parathyroidectomy, but they generally have a better clinical prognosis than do patients with FMEN I. Expand
Self-limited neonatal hyperparathyroidism in familial hypocalciuric hypercalcemia.
TLDR
Variations in clinical, hormonal and serological expressions of chronic lymphocytic thyroiditis (CLT) in children and adolescents are found in children with common endocrine diseases. Expand
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