A series of clinical cases of familial hypocalciuric hypercalcemia syndrome
https://doi.org/10.14341/probl12537
Abstract
Familial hypocalciuric hypercalcemia (FHH) - rare disease with predominantly autosomal dominant inheritance. FHH typically develops due to a heterozygous inactivating mutation in the calcium-sensitive receptor gene (CASR), less commonly due to heterozygous mutations in GNA11 and AP2S1. CASR mutations lead to an increase in the threshold for calcium sensitivity, which requires a higher concentration in serum to reduce the release of PTH. These changes are accompanied by an increase of calcium and magnesium reabsorption in the proximal tubules, which leads to hypercalcemia and hypocalciuria. Basically, FHH may be asymptomatic or accompanied by mild hypercalcemia. FHH doesn't require surgical treatment, unlike primary hyperparathyroidism (PHPT), therefore, differential diagnosis of these two conditions is extremely important. In addition, immediate relatives of a proband with FHH also require the exclusion of disease inheritance. We analyzed a series of clinical cases with a genetically confirmed diagnosis of FHH. Our clinical cases indicate a variety of clinical manifestations and the difficulties of differential diagnosis with PHPT.
About the Authors
Ju. A. Krupinova
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Julia A. Krupinova – MD.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 6279-8247
Competing Interests:
No conflict
A. A. Almaskhanova
Endocrinology Research Centre, Ministry of Health of Russia
Russian Federation
Competing Interests:
Russian Federation
Alina A. Almaskhanova - medical resident.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 8944-0460
Competing Interests:
No conflict
A. K. Eremkina
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Anna K. Eremkina - MD, PhD.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 8848-2660
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No conflict
E. E. Bibik
Endocrinology research centre
Russian Federation
Competing Interests:
Russian Federation
Ekaterina E. Bibik - MD, research associate of the Parathyroid Pathology Department.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 8522-9466
Competing Interests:
No conflict
E. V. Vasilyev
Endocrinology Research Centre
Russian Federation
Competing Interests:
Russian Federation
Evgeny V. Vasilyev - PhD in Biology, senior research associate.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 5767-1569
Competing Interests:
No conflict
N. G. Mokrysheva
Endocrinology Research centre
Russian Federation
Competing Interests:
Russian Federation
Natalia G. Mokrysheva - MD, PhD, Professor.
11 Dm. Ulyanova street, 117036 Moscow.
eLibrary SPIN: 5624-3875
Competing Interests:
No conflict
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Supplementary files
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1. Figure 1. Intracellular signaling pathways. Ca2 + and others physiological agonists, including Mg2 +, amino acids and polyamines, promote the activation of either Gαi or Gαq / 11, which lead to inhibition of adenylate cyclase and phospholipase C, respectively. The first pathway is associated with a decrease in cAMP and inhibition protein kinase A. The second promotes the synthesis of diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IF3) via CaSR-induced activation of GPCR and phospholipase C. DAG activates protein kinase C (PKC), which leads to the phosphorylation of proteins, the release calcium from the intracellular store and activation of MAPK cascades and extracellular signal kinase (ERK1 / 2): C - C-terminus of CaSR; PKA - protein kinase A; AK - amino acids; AC - adenylate cyclase; Gαi, Gα, Gβ and Gγ are different subunits of the G protein. | |
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2. Figure 2. Family history of inherited hypocalciuric hypercalcemia in patient B; Ca total. - total blood serum calcium; Ca ++ - ionized calcium; PTH - parathyroid hormone; CCCR is the ratio of renal calcium clearance to creatinine clearance. | |
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3. Figure 3. Chromatogram of CASR exon 7 - Sanger sequencing: c.1890_1894del deletion (1) and normal sequence (2). Deleted nucleotides are underlined. | |
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4. Figure 4. Chromatogram of exon 4 of CASR - Sanger sequencing: missense mutation c.554G> A. | |
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For citations:
Krupinova J.A., Almaskhanova A.A., Eremkina A.K., Bibik E.E., Vasilyev E.V., Mokrysheva N.G. A series of clinical cases of familial hypocalciuric hypercalcemia syndrome. Problems of Endocrinology. 2020;66(5):61-69. (In Russ.) https://doi.org/10.14341/probl12537
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