Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism

Pollak, Martin R.; Chou, Yah‐Huei Wu; Marx, Stephen J.; Steinmann, Beat; Cole, David E. C.; Brandi, Maria Luisa; Papapoulos, Socrates E.; Menko, Fred H.; Hendy, Geoffrey N.; Brown, Edward M.; Seidman, Christine E.; Seidman, Jonathan G.

doi:10.1016/b978-0-12-397166-1.00024-2

Cited by 10 publications

(13 citation statements)

References 158 publications

(274 reference statements)

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“…FHH is genetically heterogeneous and three different variants have been identified 73 . Most cases of FHH are caused by heterozygous inactivating mutations of CASR on 3q13.3–q21.1 (FHH type 1) 74 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

“…Recent studies have identified two additional forms of FHH linked to chromosome 19, which are due to mutations of G protein subunit all ( GNA11; FHH type 2) 75 and adaptor-related protein complex 2σ 1 subunit ( AP2S1; FFH type 3) 75 . Neonatal severe hyperparathyroidism results from inheritance of two abnormal CASR alleles in either the homozygous or the compound heterozygous state 73 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

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Primary hyperparathyroidism

Bilezikian

Cusano

Khan

et al. 2016

Nat Rev Dis Primers

215

166

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Primary hyperparathyroidism (PHPT) is a common disorder in which parathyroid hormone (PTH) is excessively secreted from one or more of the four parathyroid glands. A single benign parathyroid adenoma is the cause in most people. However, multiglandular disease is not rare and is typically seen in familial PHPT syndromes. The genetics of PHPT is usually monoclonal when a single gland is involved and polyclonal when multiglandular disease is present. The genes that have been implicated in PHPT include proto-oncogenes and tumour-suppressor genes. Hypercalcaemia is the biochemical hallmark of PHPT. Usually, the concentration of PTH is frankly increased but can remain within the normal range, which is abnormal in the setting of hypercalcaemia. Normocalcaemic PHPT, a variant in which the serum calcium level is persistently normal but PTH levels are increased in the absence of an obvious inciting stimulus, is now recognized. The clinical presentation of PHPT varies from asymptomatic disease (seen in countries where biochemical screening is routine) to classic symptomatic disease in which renal and/or skeletal complications are observed. Management guidelines have recently been revised to help the clinician to decide on the merits of a parathyroidectomy or a non-surgical course. This Primer covers these areas with particular attention to the epidemiology, clinical presentations, genetics, evaluation and guidelines for the management of PHPT.

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Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Section: Mechanisms/pathophysiologymentioning

confidence: 99%

Primary hyperparathyroidism

Bilezikian

Cusano

Khan

et al. 2016

Nat Rev Dis Primers

215

166

View full text Add to dashboard Cite

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“…Because FHH is an autosomal dominant condition, three genetic situations might be encountered by the newborns of FHH mothers: the unaffected and the heterozygous neonates might present with hypocalcaemia induced by the in utero suppression of the parathyroid, the latter being at risk of developing hypercalcemia with hypocalcaemia in the first year of life. The homozygous form of FHH results in a severe neonatal hyperparathyroidism, which requires the surgical removal of the glands during the neonatal phase [37,38].…”

Section: Fetal Consequences Of Hypercalcemiamentioning

confidence: 99%

Hypercalcemia during pregnancy: management and outcomes for mother and child

et al. 2021

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Diagnosing and treating hypercalcemia during pregnancy can be challenging due to both the physiological changes in calcium homeostasis and the underlying cause for the hypercalcemia. During pregnancy and lactation there is increased mobilization of calcium in the mother to meet the fetus’ calcium requirements. Here we discuss the diagnostic challenges, management, and patient perspective of hypercalcemia during pregnancy in two particular cases and in other rare conditions causing hypercalcemia.

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“…Heterozygous neonates born to an unaffected mother may have severe hypercalcemia caused by secondary hyperparathyroidism in utero. An homozygous or compound heterozygous neonate is at risk of neonatal severe hyperparathyroidism, requiring urgent parathyroidectomy …”

Section: Discussionmentioning

confidence: 99%

Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls

et al. 2020

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Familial hypocalciuric hypercalcemia (FHH) is a group of autosomal dominant disorders caused by dysfunction of the calcium sensing receptor (CaSR) and its downstream signaling proteins, leading to generally asymptomatic hypercalcemia. During pregnancy, distinguishing FHH from primary hyperparathyroidism (PHPT) is important, as the latter is associated with adverse outcomes and can be treated surgically during pregnancy, whereas the former is benign. This case report highlights the difficulties in diagnosing FHH during pregnancy. A 32‐year‐old woman was found to have asymptomatic hypercalcemia at 14‐weeks’ gestation. Investigations showed a corrected calcium (cCa) of 2.61 mmol/L (2.10 to 2.60), ionized Ca (iCa) of 1.40 mmol/L (1.15 to 1.28), 25OHD of 33 nmol/L (75 to 250), and PTH of 9.5 pmol/L (1.5 to 7.0). The patient was treated with 2000 IU cholecalciferol daily with normalization of 25OHD. The urine calcium / creatinine clearance ratio (CCCR) was 0.0071, and neck US did not visualize a parathyroid adenoma. Upon a retrospective review of the patient's biochemistry from 2 years prior, hypercalcemia was found that was not investigated. The patient was monitored with serial iCa levels and obstetric US. She delivered a healthy boy at 38‐weeks’ gestation. Postnatal iCa was 1.48 mmol/L and remained elevated. Her son had elevated iCa at birth of 1.46 mmol/L (1.15 to 1.33), which rose to 1.81 mmol/L by 2 weeks. He was otherwise well. Given the familial hypercalcemia, a likely diagnosis of FHH was made. Genetic testing of the son revealed a missense mutation, NM_000388.3(CASR):c.2446A > G, in exon 7 of the CaSR, consistent with FHH type 1. To our knowledge, there are only three existing reports of FHH in pregnancy. When differentiating between FHH and PHPT in pregnancy, interpretation of biochemistry requires an understanding of changes in Ca physiology, and urine CCCR may be unreliable. If the decision is made to observe, clinical symptoms, calcium levels, and fetal US should be monitored, with biochemistry and urine CCCR performed postpartum, once lactation is completed © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Familial Hypocalciuric Hypercalcemia and Neonatal Severe Hyperparathyroidism

Cited by 10 publications

References 158 publications

Primary hyperparathyroidism

Primary hyperparathyroidism

Hypercalcemia during pregnancy: management and outcomes for mother and child

Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls

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