Familial Hypocalciuric Hypercalcemia in Pregnancy: Diagnostic Pitfalls

Alicia R. Jones, Matthew J.L. Hare, Justin Brown, Jun Yang, Caroline Meyer, Frances Milat, Carolyn A. Allan

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    Familial hypocalciuric hypercalcemia (FHH) is a group of autosomal dominant disorders caused by dysfunction of the calcium sensingreceptor (CaSR) and its downstream signaling proteins, leading to generally asymptomatic hypercalcemia. During pregnancy, distin-guishing FHH from primary hyperparathyroidism (PHPT) is important, as the latter is associated with adverse outcomes and can betreated surgically during pregnancy, whereas the former is benign. This case report highlights the difculties in diagnosing FHH dur-ing pregnancy. A 32-year-old woman was found to have asymptomatic hypercalcemia at 14-weeks’ gestation. Investigations showeda 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 urinecalcium / creatinine clearance ratio (CCCR) was 0.0071, and neck US did not visualize a parathyroid adenoma. Upon a retrospectivereview of the patient’s biochemistry from 2 years prior, hypercalcemia was found that was not investigated. The patient was moni-tored with serial iCa levels and obstetric US. She delivered a healthy boy at 38-weeks’ gestation. Postnatal iCa was 1.48 mmol/Land 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. Hewas otherwise well. Given the familial hypercalcemia, a likely diagnosis of FHH was made. Genetic testing of the son revealed a mis-sense mutation, NM_000388.3(CASR):c.2446A > G, in exon 7 of the CaSR, consistent with FHH type 1. To our knowledge, there areonly three existing reports of FHH in pregnancy. When differentiating between FHH and PHPT in pregnancy, interpretation of bio-chemistry requires an understanding of changes in Ca physiology, and urine CCCR may be unreliable. If the decision is made toobserve, clinical symptoms, calcium levels, and fetal US should be monitored, with biochemistry and urine CCCR performed postpar-tum, once lactation is completed
    Original languageEnglish
    Article numbere10362
    Pages (from-to)1-5
    Number of pages5
    JournalJBMR Plus
    Issue number6
    Publication statusPublished - Jun 2020


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