ABSTRACT This case series describes the clinical spectrum, diagnostic evaluation, and treatment outcomes of four patients from two Indian families diagnosed with inactivating PTH/PTHrP signaling disorder (iPPSD), traditionally classified as pseudohypoparathyroidism (PHP). Family 1 includes two siblings: the elder brother (Case 1) presented with short stature, obesity, hypothyroidism, and carpopedal spasms, but without brachydactyly or ectopic ossifications. His sister (Case 2) exhibited brachydactyly type E, PCOS, and similar biochemical abnormalities. Genetic testing identified a Gsα mutation, consistent with iPPSD2 (formerly PHP1a). Family 2 includes two brothers: the elder (Case 3) had intermittent carpopedal spasms, while the younger (Case 4) was asymptomatic but showed biochemical evidence of PTH resistance. Genetic analysis revealed no GNAS mutations, aligning with iPPSD3 (formerly PHP1b). Treatment with active vitamin D and calcium supplementation led to symptomatic improvement and biochemical stabilization, although PTH resistance persisted. This series highlights the clinical and genetic diversity of iPPSD and underscores the importance of tailored management strategies in these complex endocrine disorders.
Jha et al. (Tue,) studied this question.