A 9-year-old girl has tetany with Chvostek sign. Calcium is 7.0 mg/dL, phosphate 6.8 mg/dL, magnesium normal, and PTH 320 pg/mL. She has round facies, short stature, brachydactyly of the fourth metacarpals, and subcutaneous calcification. Basal metabolic functions are otherwise intact. What is the underlying defect?

• A Activating mutation of the calcium-sensing receptor
• B Autoimmune destruction of the parathyroid glands
• C Resistance of target tissues to parathyroid hormone due to GNAS mutation ✓
• D Defective conversion of vitamin D to 1,25-dihydroxyvitamin D

Explanation

Albright hereditary osteodystrophy with biochemical hypoparathyroidism but elevated PTH defines pseudohypoparathyroidism type 1C, caused by a GNAS mutation producing end-organ resistance to PTH through reduced Gs-alpha activity. Autoimmune hypoparathyroidism would show low or inappropriately normal PTH. An activating calcium-sensing receptor mutation gives autosomal dominant hypocalcaemia without the skeletal phenotype, and 1-alpha-hydroxylase deficiency causes rickets rather than this dysmorphic syndrome. The key discriminator is high PTH with resistance signs.

Reference: Williams Textbook of Endocrinology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.