Significant developmental elevation in serum parathyroid hormone levels in a large kindred with familial benign (hypocalciuric) hypercalcemia

McMurtry, Cynthia T.; Schranck, Francine W.; Walkenhorst, Denise A.; Murphy, William A.; Kocher, David B.; Teitelbaum, Steven L.; Rupich, Reta; Whyte, Michael P.

doi:10.1016/0002-9343(92)90229-5

Cited by 92 publications

(33 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One further paper was excluded because the mutation identi¢ed was a rare variant rather than a CaSR mutation. 41 The ranges of results from these four excluded papers appeared very similar to those found in our meta-analysis.…”

Section: Laboratory Features Of Fbhhsupporting

confidence: 78%

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

Gunn

Gaffney

2004

Ann Clin Biochem

View full text Add to dashboard Cite

Mutations in the calcium-sensing receptor gene (CaSR) may result in disorders of calcium homeostasis manifesting as familial benign hypocalciuric hypercalcaemia (FBHH), neonatal severe hyperparathyroidism (NSHPT) or autosomal dominant hypocalcaemia with hypercalciuria (ADHH). FBHH may have a population prevalence as high as one in 16 000, and ADHH one in 70 000. NSHPT is very rare.The FBHH condition is usually asymptomatic. Parathyroidectomy does not result in normal serum calcium, and no active treatment is indicated. To differentiate FBHH from primary hyperparathyroidism (PHPT), a guideline which includes measurement of serum calcium, intact parathyroid hormone (PTH), magnesium and fasting urinary calcium excretion is proposed. Screening of family members for hypercalcaemia, and occasionally a search for mutations in the CaSR gene, may be required.The NSHPT condition may manifest with hypercalcaemia, (usually) very elevated serum PTH concentration, subperiosteal erosions and fractures. Milder cases may be managed medically, but respiratory failure, extreme hypercalcaemia and failure to thrive are indications for early parathyroidectomy.The ADHH condition may result in asymptomatic hypocalcaemia, but some affected family members have minor symptoms, and a minority experience seizures in infancy which can recur into adulthood. A significant proportion of cases previously reported as idiopathic hypoparathyroidism (IHP) may in fact be due to mutations in the CaSR gene. In a moderately hypocalcaemic patient with no other clearly discernible cause, an elevated urine calcium:creatinine ratio is suggestive of ADHH, as is the presence of a first-degree relative with hypocalcaemia. If treatment with vitamin D analogues is undertaken, serum and urine calcium should be monitored, advice which applies equally to ADHH and IHP.

show abstract

Section: Laboratory Features Of Fbhhsupporting

confidence: 78%

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

Gunn

Gaffney

2004

Ann Clin Biochem

View full text Add to dashboard Cite

show abstract

“…In two small cross-sectional studies, intact PTH values above the reference limits were only demonstrable in FHH patients older than 30 years of age. 26,27 This probably indicates that the rise in intact PTH with ageing in FHH is due to the superimposed development of age-related secondary hyperparathyroidism in addition to the mutational resetting of the CaSR threshold. Thus, intact PTH values which are elevated above the reference limits in young (< 30 years old) individuals and intact PTH results more than two fold elevated above the reference limits in older (> 30 years old) individuals make the diagnosis of FHH unlikely.…”

Section: Recommendations For Australian Laboratoriesmentioning

confidence: 99%

Diagnosis of primary hyperparathyroidism: controversies, practical issues and the need for Australian guidelines

Glendenning¹

2003

Internal Medicine Journal

View full text Add to dashboard Cite

Primary hyperparathyroidism (PHPT) is one of the most common endocrine disease processes, however the clinical presentation in 2003 is typically characterized by minimal signs or symptoms of hypercalcaemia or para-thyroid hormone (PTH) excess. Recent developments in imaging and management of PHPT have been published, however the area of biochemical investigation has been relatively neglected. A group of experts convened in April 2002 to consider whether changes were needed to the 1990 consensus guidelines which defined criteria for the diagnosis and management of asymptomatic PHPT. It is appropriate to review the revised recommendations, which have been disseminated by the panel and were recently published. Each of the laboratory -analytes used to establish the diagnosis of PHPT and exclude alternative diagnoses or complications will be considered in succession in this review: (i) calcium, (ii) intact PTH, (iii) urinary calcium and (iv) 25 hydroxy-vitamin D. Furthermore, critical appraisal of the new diagnostic criteria and their applicability to Australian laboratories will be addressed. Finally, limitations and problems associated with the measurement of each analyte will be reviewed.

show abstract

“…Furthermore, although one of the typical features of FHH is hypocalciuria, some patients may present with hypercalciuria caused by the distinct functions of the mutated CaSR in renal and parathyroid cells leading to the incorrect diagnosis of primary HPT (24). Further, due to the tissue-specific CaSR-mediated signaling pathways, patients with FHH can manifest uncommon complications like pancreatitis, osteomalacia, and nephrolithiasis (24,25,26) that are not expected in this otherwise benign condition.…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

Papadopoulou

Gole²,

Melachroinou³

et al. 2016

Jcrpe

View full text Add to dashboard Cite

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder, associated with inactivating mutations of the calcium-sensing receptor (CaSR). To evaluate the functional significance of a CaSR mutation, identified in a young infant who presented with hypercalcemia and hypocalciuria. The CaSR gene coding sequences were analyzed by polymerase chain reaction amplification and direct sequencing analysis. The mutation identified was introduced by site-directed mutagenesis into a wild-type (WT) CaSR plasmid, and human embryonic kidney 293 T cells were transfected with either the WT or mutant CaSR. The function of the mutated CaSR protein was analyzed by evaluating the free intracellular calcium [(Ca2+)i] response after challenge with extracellular calcium (Ca2+). We identified a heterozygous mutation c.772_773delGTinsA in exon 4 resulting in the substitution of amino acid valine (Val) with amino acid arginine (Arg) and the premature pause of the translation 46 amino acids later (Val258ArgfsTer47). Functional assay showed that cells transfected with the mutant CaSR had a significantly poorer response to extracellular Ca2+ stimulation compared with the WT. We have shown that the c.772_773delGTinsA mutation causes a significant alteration of CaSR function leading to features of FHH in an affected young infant since the first months of life.

show abstract

Significant developmental elevation in serum parathyroid hormone levels in a large kindred with familial benign (hypocalciuric) hypercalcemia

Cited by 92 publications

References 28 publications

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

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

Diagnosis of primary hyperparathyroidism: controversies, practical issues and the need for Australian guidelines

Identification and Functional Characterization of a Calcium-Sensing Receptor Mutation in an Infant with Familial Hypocalciuric Hypercalcemia

Contact Info

Product

Resources

About