Journal of Interdisciplinary Genomics

Interdisciplinary Society of Genetic & Genomic Medicine (유전의학융합회)
권호 표지
DOI QR코드

DOI QR Code

Pseudohypoparathyroidism: Clinical Review of Diagnosis and Genetic Etiology

  • Kyung Mi Jang (Department of Pediatrics, Yeungnam University School of Medicine, Yeungnam University Hospital)
  • Received : 2023.10.10
  • Accepted : 2023.10.30
  • Published : 2023.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Pseudohypoparathyroidism (PHP) is very rare and shows heterogeneity with impaired genetic components. PHP is characterized by parathyroid hormone resistance to target organ, related with a GNAS (guanine nucleotide-binding protein α-subunit) mutation and epimutation. PHP receptor is coupled with the stimulatory G protein which activates cyclic adenosine monophosphate formation. PHP type 1A is caused by inactivating mutations on the maternal allele of the GNAS whereas paternal allele mutations cause pseudopseudohypoparathyroidism. PHP type 1B is caused by abnormal patterns of methylation in differentially methylated region which can be divided into partial or complete. This disease has some difficulties to diagnose according to these different molecular alterations caused by complex genetic and epigenetic defects. According to this different molecular alterations, genetic confirmation must be done to discriminate their etiology.

Keywords

References

  1. Nakamura Y, Matsumoto T, Tamakoshi A, Kawamura T, Seino Y, Kasuga M, et al. Prevalence of idiopathic hypoparathyroidism and pseudohypoparathyroidism in Japan. J Epidemiol 2000;10:29-33. doi: 10.2188/jea.10.29.
  2. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L. Pseudohypoparathyroidism - epidemiology, mortality and risk of complications. Clin Endocrinol (Oxf) 2016;84:904-11. doi: 10.1111/cen.12948.
  3. 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. Nature Reviews Endocrinology 2018;14:476-500. doi: 10.1038/s41574-018-0042-0.
  4. Cheloha RW, Gellman SH, Vilardaga JP, Gardella TJ. PTH receptor-1 signalling-mechanistic insights and therapeutic prospects. Nat Rev Endocrinol 2015;11:712-24. doi: 10.1038/nrendo.2015.139.
  5. Mannstadt M, Juppner H, Gardella TJ. Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol 1999;277:F665-75. doi: 10.1152/ajprenal.1999.277.5.F665.
  6. Wilson LC, Hall CM. Albright's hereditary osteodystrophy and pseudohypoparathyroidism. Semin Musculoskelet Radiol 2002;6:273-83. doi: 10.1055/s-2002-36726.
  7. Goswami M, Verma M, Singh A, Grewal H, Kumar G. Albright hereditary osteodystrophy: a rare case report. Journal of Indian Society of Pedodontics and Preventive Dentistry 2009;27:184-8. doi: 10.4103/0970-4388.57101.
  8. Hwang SK, Shim YJ, Oh SH, Jang KM. Early diagnosis of pseudohypoparathyroidism before the development of hypocalcemia in a young infant. Children (Basel) 2022;9. doi: 10.3390/ children9050723.
  9. Germain-Lee EL. Management of pseudohypoparathyroidism. Curr Opin Pediatr 2019;31:537-49. doi: 10.1097/mop.0000000000000783.
  10. Lu D, Dong A, Zhang J, Guo X. A novel GNAS mutation in pseudohypoparathyroidism type 1a in a Chinese man presented with recurrent seizure: a case report. BMC Endocrine Disorders 2021; 21:12. doi: 10.1186/s12902-020-00651-z.
  11. Bastepe M. The GNAS locus and pseudohypoparathyroidism. Adv Exp Med Biol 2008;626:27-40. doi: 10.1007/978-0-387-77576-0_3.
  12. Simpson C, Grove E, Houston BA. Pseudopseudohypoparathyroidism. The Lancet 2015;385:1123. doi: 10.1016/S0140-6736(14)61640-8.
  13. Aldred MA, Trembath RC. Activating and inactivating mutations in the human GNAS1 gene. Hum Mutat 2000;16(3):183-9. doi: 10.1002/1098-1004(200009)16:3<183::AID-HUMU1>3.0.CO;2-L.
  14. Mantovani G. Pseudohypoparathyroidism: diagnosis and treatment. The Journal of Clinical Endocrinology & Metabolism 2011; 96:3020-30. doi: 10.1210/jc.2011-1048.
  15. Matta-Coelho C, Mesquita J, Souto SB. Pseudohypoparathyroidism Type 1B with Asymptomatic Hypocalcemia. AACE Clinical Case Reports 2018;4:249-51. doi: 10.4158/ACCR-2017-0064.
  16. Shoemaker AH, Juppner H. Nonclassic features of pseudohypoparathyroidism type 1A. Curr Opin Endocrinol Diabetes Obes 2017;24:33-8. doi: 10.1097/med.0000000000000306.
  17. Bastepe M, Frohlich LF, Hendy GN, Indridason OS, Josse RG, Koshiyama H, et al. Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS. The Journal of Clinical Investigation 2003;112:1255-63. doi: 10.1172/JCI19159.
  18. Poradosu S, Bravenboer B, Takatani R, Juppner H. Pseudohypoparathyroidism type 1B caused by methylation changes at the GNAS complex locus. BMJ Case Rep 2016;2016. doi: 10.1136/bcr-2016-214673.