Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
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Stine Linding Andersen
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Anja Lisbeth Frederiksen
Abstract
Objectives
Hypoparathyroidism is a rare disorder which is predominantly of idiopathic or genetic origin in children. The diagnosis is made from the biochemical measurement of parathyroid hormone (PTH), and the key findings include a low PTH in combination with hypocalcemia and hyperphosphatemia. However, the level of PTH encountered in patients with hypoparathyroidism may be dependent on the underlying genetic cause of the disorder as well as the biochemical assay used for assessment of PTH.
Case presentation
A three-year-old child with asymptomatic primary hypoparathyroidism was identified with a homozygous missense variant of PTH. A sudden unexpected high PTH result after a shift from 2nd to 3rd generation PTH assay in the routine laboratory provided a clue on the underlying genetic etiology.
Conclusions
Pathogenic variants of PTH as a cause of hypoparathyroidism are rarely described. In this case, the child was asymptomatic, and discordant PTH results were seen with different assays.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Clarke, BL, Brown, EM, Collins, MT, Jüppner, H, Lakatos, P, Levine, MA, et al.. Epidemiology and diagnosis of hypoparathyroidism. J Clin Endocrinol Metab 2016;101:2284–99. https://doi.org/10.1210/jc.2015-3908.Suche in Google Scholar PubMed PubMed Central
2. Underbjerg, L, Sikjaer, T, Mosekilde, L, Rejnmark, L. The epidemiology of nonsurgical hypoparathyroidism in Denmark: a nationwide case finding study. J Bone Miner Res 2015;30:1738–44. https://doi.org/10.1002/jbmr.2501.Suche in Google Scholar PubMed
3. Kim, JH, Shin, YL, Yang, S, Cheon, CK, Cho, JH, Lee, BH, et al.. Diverse genetic aetiologies and clinical outcomes of paediatric hypoparathyroidism. Clin Endocrinol 2015;83:790–6. https://doi.org/10.1111/cen.12944.Suche in Google Scholar PubMed
4. Lee, JH, Davaatseren, M, Lee, S. Rare PTH gene mutations causing parathyroid disorders: a review. Endocrinol Metab 2020;35:64–70. https://doi.org/10.3803/enm.2020.35.1.64.Suche in Google Scholar PubMed PubMed Central
5. Cavalier, E, Vasikaran, S, Bhattoa, HP, Heijboer, AC, Makris, K, Ulmer, CZ. The path to the standardization of PTH: is this a realistic possibility? A position paper of the IFCC C-BM. Clin Chim Acta 2021;515:44–51. https://doi.org/10.1016/j.cca.2020.12.022.Suche in Google Scholar PubMed PubMed Central
6. Dupuy, AM, Bargnoux, AS, Morena, M, Lauret, E, Souberbielle, JC, Cavalier, E, et al.. Moving from the second to the third generation Roche PTH assays: what are the consequences for clinical practice? Clin Chem Lab Med 2019;57:244–9. https://doi.org/10.1515/cclm-2018-0300.Suche in Google Scholar PubMed
7. Lee, S, Mannstadt, M, Guo, J, Kim, SM, Yi, H-S, Khatri, A, et al.. A homozygous [Cys25]PTH(1-84) mutation that impairs PTH/PTHrP receptor activation defines a novel form of hypoparathyroidism. J Bone Miner Res 2015;30:1803–13. https://doi.org/10.1002/jbmr.2532.Suche in Google Scholar PubMed PubMed Central
8. Jüppner, H. Molecular definition of pseudohypoparathyroidism variants. J Clin Endocrinol Metab 2021;106:1541–52.10.1210/clinem/dgab060Suche in Google Scholar PubMed PubMed Central
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
Artikel in diesem Heft
- Frontmatter
- Review Article
- Impact of Obesity on Bone Metabolism in Children
- Mini Review
- Late sequelae of drug reaction with eosinophilia and systemic symptoms (DRESS) cause thyroid dysfunction and thyroiditis: review of literature
- Original Articles
- Moderating effect of bone maturation on the relationship between body fat and insulin resistance
- Prevalence of nephropathy in Indian children and youth with type 1 diabetes mellitus
- Initial neutrophil/lymphocyte and lymphocyte/monocyte ratios can predict future insulin need in newly diagnosed type 1 diabetes mellitus
- Subcutaneous adipose tissue is a positive predictor for bone mineral density in prepubertal children with Prader–Willi syndrome independent of lean mass
- The attitudes, experiences, and self-competencies of pediatric endocrinology fellows and attending physicians regarding diabetes technology: the Turkey experience
- Adiposity measures in screening for metabolic syndrome among Chinese children and adolescents
- Increased anxiety symptoms in pediatric type 1 diabetes during the acute phase of COVID-19 lockdown
- Pediatric adrenal insufficiency: thirty years experience at a Portuguese hospital
- Spectrum of PAH gene mutations and genotype–phenotype correlation in patients with phenylalanine hydroxylase deficiency from Turkey
- Serum spexin levels are not associated with size at birth but are associated with metabolic syndrome components in prepubertal children born at term
- Familial early-onset obesity in Turkish children: variants and polymorphisms in the melanocortin-4 receptor (MC4R) gene
- An update of the mutation spectrum of phenylalanine hydroxylase (PAH) gene in the population of Turkey
- Primary hypertriglyceridemia induced pancreatitis in a cohort of Pakistani children
- Investigation of the relationship between serum sclerostin and dickkopf-1 protein levels with bone turnover in children and adolescents with type-1 diabetes mellitus
- Case Reports
- Diagnostic value of plasma lysosphingolipids levels in a Niemann–Pick disease type C patient with transient neonatal cholestasis
- A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity
- Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
- Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age
