A patient with pseudohypoparathyroidism type 1a (Albright hereditary osteodystrophy) has elevated PTH but hypocalcemia. What is the biochemical defect?

• A Deficiency of PTH itself
• B Absence of PTH receptors on renal tubular cells
• C Defective vitamin D receptor in target organs
• D Loss-of-function mutation in Gsα protein preventing cAMP generation ✓

Explanation

Pseudohypoparathyroidism type 1a is caused by heterozygous inactivating mutations in GNAS1 encoding Gsα protein. PTH binds its receptor (PTHR1, a Gs-coupled GPCR) normally, but downstream Gsα-mediated adenylyl cyclase activation is blunted, reducing cAMP generation in renal tubular cells and osteoblasts. This prevents phosphaturia and calcium mobilization. PTH levels are elevated (elevated PTH in response to hypocalcemia) with end-organ resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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