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CASE REPORT article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1415639
This article is part of the Research Topic Molecular Mechanisms and Treatment of Monogenic Skeletal Disorders View all 3 articles

Familial hypoparathyroidism with elevated parathyroid hormone due to an inactivating PTH mutation responsive to Teriparatide

Provisionally accepted
Noha Mukhtar Noha Mukhtar Balgees Alghamdi Balgees Alghamdi Meshael Al Swailem Meshael Al Swailem Afaf Alsaghier Afaf Alsaghier Ali S. Alzahrani Ali S. Alzahrani *
  • King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

The final, formatted version of the article will be published soon.

    Introduction: Only 11 PTH mutations have been described as causes of familial isolated hypoparathyroidism (FIH). In this report, we describe a family with FIH but with significant elevation of functionally inactive PTH due to a PTH mutation. We also show a positive therapeutic outcome of recombinant human PTH (teriparatide) therapy in one of the siblings who was not well controlled on large doses of calcitriol and calcium replacement therapy.The proband is a 34-year-old lady who has a history of chronic severe hypocalcemia (HypoCa) since birth. She and her three brothers (33-year-old male twins, and a 21year-old male) were diagnosed with pseudohypoparathyroidism type 1b (PHPT 1b) based on the presence of chronic HypoCa (serum Ca 1.6-1.85 mmol/l) since birth associated with significantly elevated plasma PTH levels in the range of 310-564 pg/dl (normal range 10-65) and absence of signs of Albright hereditary osteodystrophy.Molecular studies: WES showed no pathogenic, likely pathogenic or variants of unknown significance in any known calcium-associated genetic disorder but a bi-allelic variant in the PTH itself (PTH, exon3: c.128G>A, p.Gly43Glu). This was confirmed by Sanger sequencing in the patient and her affected brothers.Because the patient's HypoCa was not controlled on large doses of calcitriol and calcium carbonate, a trial of teriparatide 20 mcg SC daily was started and resulted in normalization of calcium, decline in PTH levels and significant improvement in her general wellbeing.High PTH in the presence of congenital hypocalcemia is not always due to receptor or post-receptor defect and can be due to a biologically inactive mutated PTH. In such cases, treatment with teriparatide may result in stabilization of biochemical profile and improvement in quality of life.

    Keywords: Hypoparathyroidism, familial hypoparathyroidism, Hypocalcemia, Parathyroid Hormone, PTH, Mutation

    Received: 10 Apr 2024; Accepted: 18 Sep 2024.

    Copyright: © 2024 Mukhtar, Alghamdi, Al Swailem, Alsaghier and Alzahrani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ali S. Alzahrani, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

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