Pseudohypoparathyroidism
- 1. The pseudos Pseudo from the greek – false or lying Samantha Harrison MBBS 3 KCL
- 2. Pseudohypoparathyroidism Definition: Characterised by a peripheral resistance to parathyroid hormone rather than a deficiency Hypocalcaemia, hyperphosphataemia, raised serum PTH Three Types: 1a, 1b, 2 Epidemiology: F:M ratio – 2:1 Only prevalence study – Japan (1998) – 3.4 cases per million Any age can be affected
- 3. Etiology Collection of Autosomal Dominant inherited genetic conditions All heterozygous Haploinsufficiency of GNAS1 – only 1 copy of the normal protein. It is not fatal but cannot continue normal functioning
- 4. Pseudohypoparathyroidism: Type 1a Signs and Symptoms Type 1a Short 4th and 5th metacarpals, round face, short stature, calcium deposits under the skin, dimples, stocky habitus, developmental delay, dental hypoplasia, soft tissue calcification/ossification Also called Albright hereditary dystrophy Associated with TSH resistance, hypogonadism, females often suffer impaired fertility, oligomenorrhea, delayed puberty, male – infertility
- 6. Pathophysiology Molecular defect in gene (GNAS1) GNAS1 encodes the alpha subunit of the stimulatory G protein (Gsa) Gsa is involved with: thyrotropin, antidiuretic hormone, the gonadotropins, glucagon, adrenocorticotropin, and growth hormone–releasing hormone. Also can affect senses
- 7. Type 1b Pathophysiology of Type 1b is by the same mechanism (GNAS1) leading to Gsa defect. Characterised by only renal resistance to parathyroid hormone, otherwise endocrinologically normal Sufferers are variably affected Paternal imprinting.
- 8. Type II Type II is characterised by a low calcium and high phosphate levels Therefore tissues are resistant to parathyroid hormone However, type II is not characterised by any skeletal changes or the phenotypic appearance of Type 1a All different physiologies are due to differences in the imprinting defect.
- 9. Pseudopseudohypoparathyroidism Phenotypic appearance mimicking those of pseudoparathyroidism type 1a No lack of parathyroid hormone, no peripheral resistance to PTH – biochemically normal Also caused by a defect in the GNAS1 First described by Fuller Albright in 1952 http://www.toptenz.net/top-10-longest- words-in-the-english-language.php