A patient with pseudohypoparathyroidism type 1a has hypocalcaemia and elevated PTH but shows no response to exogenous PTH. The molecular defect is in:

• A PTH receptor extracellular binding domain
• B Adenylyl cyclase catalytic subunit
• C Protein kinase A regulatory subunit
• D Gs alpha subunit (GNAS1 mutation) coupling receptor to adenylyl cyclase ✓

Explanation

Pseudohypoparathyroidism type 1a (Albright hereditary osteodystrophy) results from inactivating mutations in GNAS1 encoding Gs-alpha, preventing receptor-stimulated cAMP generation; PTH binds its receptor normally but cannot transduce the signal. Mutations in the receptor itself would be type 1b. Adenylyl cyclase and PKA mutations cause different phenotypes. The hallmark is resistance to multiple Gs-coupled hormones.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.