A 16-year-old girl has short stature, round face, obesity, subcutaneous ossifications, and shortening of the fourth and fifth metacarpals. Serum calcium is 7.6 mg/dL, phosphate 5.8 mg/dL, and intact PTH 320 pg/mL (normal 15 to 65). Renal function is normal. The underlying defect is:

• A Deficient parathyroid hormone secretion
• B Vitamin D receptor mutation causing hereditary vitamin D resistant rickets
• C Activating mutation of the calcium-sensing receptor
• D Resistance to parathyroid hormone due to GNAS mutation with defective Gsα signalling ✓

Explanation

Albright hereditary osteodystrophy with biochemical hypocalcaemia, hyperphosphataemia, and frankly elevated PTH defines pseudohypoparathyroidism type 1a, caused by maternal GNAS mutations producing end-organ resistance to PTH. Distinguishing it from simple hypoparathyroidism, where PTH would be low, is the key discriminator. Activating CASR mutations cause autosomal dominant hypocalcaemia, and VDR mutations produce rickets with secondary (not this magnitude of) PTH elevation and rachitic bone changes.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.