Pseudohypoparathyroidism type 1A is a rare, autosomal dominant syndrome caused by loss-of-function mutation in the GNAS1 gene. It specifically requires maternal transmission of the mutation to result in this clinical syndrome. This mutation leads to an inability to activate adenyl cyclase when parathyroid hormone (PTH) binds to its receptor. Affected patients have a series of clinical findings otherwise known as Albright hereditary osteodystrophy. These include short stature, obesity, round face, brachydactyly, subcutaneous ossifications, hypocalcemia, and hyperphosphatemia with elevated circulating PTH and osteitis fibrosa. This disease primarily presents in childhood.
In addition to PTH resistance, affected individuals also demonstrate resistance to thyrotropin (TSH), luteinizing hormone, follicle-stimulating hormone, and gonadotropin-releasing hormone. This is due to GNAS1 expression in the thyroid, gonads, and pituitary gland.
ICD10CM: E20.1 – Pseudohypoparathyroidism
SNOMEDCT: 58833000 – Pseudohypoparathyroidism type I A
Differential Diagnosis & Pitfalls
Differential diagnoses of hypocalcemia with high PTH: