Pseudohypoparathyroidism type 1B (PHP1B), a rare disorder encountered in adolescence
-
Elpis-Athina Vlachopapadopoulou
,
Elli Anagnostou
Abstract
Objectives
The objective of this paper is to report a peculiar case of a patient with pseudohypoparathyroidism type 1b (PHP1B). Pseudohypoparathyroidism (PHP) refers to a group of disorders characterized by hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH) concentrations as the result of end-organ unresponsiveness to PTH.
Case presentation
We present a 14-year-old boy, who was admitted with severe symptomatic hypocalcaemia, absence of dysmorphic features and Albright's hereditary osteodystrophy features. Laboratory investigations revealed markedly low serum calcium, high phosphate, markedly elevated PTH levels and vitamin D insufficiency, while magnesium, albumin, ALP and TSH were normal. The clinical and laboratory findings were consistent with PHP1B. Molecular analysis revealed loss of methylation at the AB DMR of the GNAS locus, confirming the diagnosis. Yet no STX16 deletion was detected.
Conclusions
It is possible that delSTX16- patients carry a defect in an element that controls the methylation both at the GNAS-A/B DMR and at the GNAS-AS2. This rare case emphasizes the need of individualized molecular analysis in PHP1B patients in order to elucidate the possible molecular defect.
Acknowledgments
The authors would like to thank D.J.G. Mackay (Reader in Human Genetics, Faculty of Medicine, University of Southampton, UK) for her expert opinion and scientific support.
Research funding: None declared.
Author contributions: (I) Conception and design: Elpida Vlachopapadopoulou, Stephanos Michalacos, Maria Tsolia, Kyriaki Karavanaki; (II) Collection and assembly of data: Elli Anagnostou, Eirini Dikaiakou; (III) Data analysis and interpretation: Patrick Hanna, Agnes Linglart; (IV) Manuscript writing: All authors; (V). All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Conflict of interest: The authors have no conflict of interest to disclose, and no other funding or financial relationship.
Informed consent: Informed consent was obtained from the patient and all members of his family included in the study.
Ethical approval:The research has been complied with all the relevant national regulations, institutional policies and in accordance the tenets of the Helsinki Declaration, and has been approved by the institutional ethics committee of Children’s Hospital “P. & A. Kyriakou”, Athens, Greece.
References
1. Mantovani, G, Bastepe, M, Monk, D, de Sanctis, L, Thiele, S, Usardi, A, et al. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol 2018; 14: 476–500. https://doi.org/10.1038/s41574-018-0042-0.Search in Google Scholar PubMed PubMed Central
2. Fernandez, M, Jose Zambrano, M, Riquelme, J, Castiglioni, C, Kottler, M-L, Jüppner, H, et al. Pseudohypoparathyroidism type 1B associated with assisted reproductive technology. J Pediatr Endocrinol Metab 2017 Oct 26;30:1125–32. https://doi.org/10.1515/jpem-2017-0226.Search in Google Scholar PubMed PubMed Central
3. Tafaj, O, Jüppner, H. Pseudohypoparathyroidism: one gene, several syndromes. J Endocrinol Invest 2017; 40: 347–56. https://doi.org/10.1007/s40618-016-0588-4.Search in Google Scholar PubMed
4. Thiele, S, Mantovani, G, Barlier, A, Boldrin, V, Bordogna, P, De Sanctis, L, et al. From Pseudohypoparathyroidism to inactivating PTH/PTHrP Signalling Disorder (iPPSD), a novel classification proposed by the European EuroPHP network. Eur J Endocrinol 2016; 175: P1–17. https://doi.org/10.1530/eje-16-0107.Search in Google Scholar PubMed
5. Li, Y, Tollefsbol, TO. DNA methylation detection: bisulfite genomic sequencing analysis. Methods Mol Biol 2011; 791: 11–21. https://doi.org/10.1007/978-1-61779-316-5_2.Search in Google Scholar PubMed PubMed Central
6. Chong, PL, Meeking, DR. Pseudohypoparathyroidism: a rare but important cause of hypocalcaemia. BMJ Case Rep 2013;2013. https://doi.org/10.1136/bcr-2012-008040.Search in Google Scholar PubMed PubMed Central
7. Liu, J, Litman, D, Rosenberg, MJ, Yu, S, Biesecker, LG, Weinstein, LS. A GNAS1 imprinting defect in pseudohypoparathyroidism type IB. J Clin Invest 2000; 106: 1167–74. https://doi.org/10.1172/jci10431.Search in Google Scholar PubMed PubMed Central
8. Mackay, DJ, Eggermann, T, Buiting, K, Garin, I, Netchine, I, Linglart, A, et al. Multilocus methylation defects in imprinting disorders. Biomol Concepts 2015; 6: 47–57. https://doi.org/10.1515/bmc-2014-0037.Search in Google Scholar PubMed
9. Elli, FM, deSanctis, L, Ceoloni, B, Barbieri, AM, Bordogna, P, Beck-Peccoz, P, et al. Pseudohypoparathyroidism type Ia and pseudo-pseudohypoparathyroidism: the growing spectrum of GNAS inactivating mutations. Hum Mutat 2013; 34: 411–6. https://doi.org/10.1002/humu.22265.Search in Google Scholar PubMed
10. Elli, FM, de Sanctis, L, Bollati, V, Tarantini, L, Filopanti, M, Barbieri, AM, et al. Quantitative analysis of methylation defects and correlation with clinical characteristics in patients with pseudohypoparathyroidism type I and GNAS epigenetic alterations. J Clin Endocrinol Metab 2014; 99: E508–17. https://doi.org/10.1210/jc.2013-3086.Search in Google Scholar PubMed
11. Garin, I, Mantovani, G, Aguirre, U, Barlier, A, Brix, B, Elli, FM, et al. European guidance for the molecular diagnosis of pseudohypoparathyroidism not caused by point genetic variants at GNAS: an EQA study. Eur J Hum Genet 2015; 23: 438–44. https://doi.org/10.1038/ejhg.2014.127.Search in Google Scholar PubMed PubMed Central
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Articles in the same Issue
- Frontmatter
- Review Article
- The influence of growth hormone therapy on the cardiovascular system in Turner syndrome
- Original Articles
- Clinical utility of urinary gonadotrophins in hypergonadotrophic states as Turner syndrome
- Sclerostin and osteoprotegerin: new markers of chronic kidney disease mediated mineral and bone disease in children
- Monthly intravenous alendronate treatment can maintain bone strength in osteogenesis imperfecta patients following cyclical pamidronate treatment
- Mechanisms and early patterns of dyslipidemia in pediatric type 1 and type 2 diabetes
- Frequency of thyroid dysfunction in pediatric patients with congenital heart disease exposed to iodinated contrast media – a long-term observational study
- Effect of growth hormone therapy on thyroid function in isolated growth hormone deficient and short small for gestational age children: a two-year study, including on assessment of the usefulness of the thyrotropin-releasing hormone (TRH) stimulation test
- Clinical relevance of T lymphocyte subsets in pediatric Graves’ disease
- Long-term follow-up of differentiated thyroid carcinoma in children and adolescents
- A quality improvement project for managing hypocalcemia after pediatric total thyroidectomy
- Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil
- Clinical characteristics, surgical approach, BRAFV600E mutation and sodium iodine symporter expression in pediatric patients with thyroid carcinoma
- BRAFV600E and TERT promoter mutations in paediatric and young adult papillary thyroid cancer and clinicopathological correlation
- Case Reports
- Pseudohypoparathyroidism type 1B (PHP1B), a rare disorder encountered in adolescence
- Impaired glucose homeostasis and a novel HLCS pathogenic variant in holocarboxylase synthetase deficiency: a report of two cases and brief review
- Transcobalamin II deficiency in twins with a novel variant in the TCN2 gene: case report and review of literature
- Aldosterone deficiency with a hormone profile mimicking pseudohypoaldosteronism
- Non-classical lipoid adrenal hyperplasia presenting as hypoglycemic seizures
