Familial hypocalciuric hypercalcemia in an index male: grey zones of the differential diagnosis from primary hyperparathyroidism in a 13-year clinical follow up

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023761%3A_____%2F20%3AN0000038" target="_blank" >RIV/00023761:_____/20:N0000038 - isvavai.cz</a>

Result on the web

<a href="http://www.biomed.cas.cz/physiolres/pdf/2020/69_S321.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/2020/69_S321.pdf</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Familial hypocalciuric hypercalcemia in an index male: grey zones of the differential diagnosis from primary hyperparathyroidism in a 13-year clinical follow up

Original language description

Familial hypocalciuric hypercalcemia (FHH) type 1, caused by a heterozygous inactivating mutation of the gene encoding the calcium-sensing receptor (CaSR), is characterized by mild to moderate hypercalcemia, hypocalciuria and inappropriately normal or elevated parathyroid hormone (PTH). FHH must be differentiated from primary hyperparathyroidism (PHPT) because parathyroidectomy is ineffective in the former. Herein, we report a 39-year-old male patient with a 13-year history of asymptomatic PTH-dependent hypercalcemia (mean calcium of 2.88 mmol/l; reference range 2.15-2.55 mmol/l) and calcium-to-creatinine clearance ratio (Ca/Cr) ranging from 0.007 to 0.0198, which is consistent with either FHH or PHPT. Although a family history of hypercalcemia was negative, and PET-CT with fluorocholine was suggestive of a parathyroid adenoma, genetic analysis of the CaSR gene identified a heterozygous inactivating mutation NM_000388.4:c.1670G>A p. (Gly557Glu) in exon 6 and a polymorphism NM_000388.4:c.1192G>A p. (Asp398Asn) in exon 4. The G557E mutation has been previously reported in a Japanese family in which all family members with the mutation had Ca/Cr below 0.01 consistent with FHH. The biochemical profile of FHH and PHPT may overlap. Our FHH patient with a G557E CaSR mutation illustrates that the differential diagnosis can be difficult in an index case with no family history, (false) positive parathyroid imaging and higher calciuria than expected for FHH. Calcium intake, vitamin D status and bone resorption might have contributed to the Ca/Cr variations over a 13-year clinical follow up. This case thus emphasizes the irreplaceable role of genetic testing of the CaSR gene when clinical evaluation is inconclusive.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30105 - Physiology (including cytology)

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

1802-9973

Volume of the periodical

69

Issue of the periodical within the volume

Supplement 2

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

8

Pages from-to

"S-321"-"S-328"

UT code for WoS article

000581646000016

EID of the result in the Scopus database

2-s2.0-85094569774