A 16-year-old girl has short stature, a round face, obesity, and shortening of the fourth and fifth metacarpals. Serum calcium is 7.8 mg/dL, phosphate 5.6 mg/dL, and PTH 320 pg/mL. She also has mild intellectual disability. Which defect best explains these findings?

• A Calcium-sensing receptor gain-of-function mutation
• B GNAS mutation causing end-organ resistance to parathyroid hormone ✓
• C 25-hydroxyvitamin D-1-alpha hydroxylase deficiency
• D PTH gene mutation causing biologically inactive hormone

Explanation

Albright hereditary osteodystrophy with hypocalcaemia, hyperphosphataemia, and elevated PTH defines pseudohypoparathyroidism type 1a, caused by maternal GNAS mutations that impair Gs alpha signalling and produce renal resistance to PTH. The same skeletal phenotype with normal calcium and PTH is pseudopseudohypoparathyroidism, a tempting distractor ruled out by the abnormal biochemistry here. Calcium-sensing receptor activating mutations cause autosomal dominant hypocalcaemia without this body habitus.

Reference: Williams Textbook of Endocrinology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.