[Clinical and genetic characteristics of pseudohypoparathyroidism type 1]

A retrospective study was conducted to include patients with genetically confirmed pseudohypoparathyroidism (PHP) type 1 at the First Affiliated Hospital of Zhengzhou University from August 2016 to April 2025, aiming to analyze their clinical and genetic characteristics. A total of 15 patients with PHP type 1 were enrolled, including 7 males and 8 females, with a median age of onset at 12.0 years (range: 3.5-40.0 years). Among them, 4 cases were PHP 1A and 11 cases were PHP 1B. All patients exhibited elevated parathyroid hormone levels, and 14 had hypocalcemia. Hyperphosphatemia was observed in all pediatric patients, while serum phosphate levels were normal in adult patients. Six patients had hypokalemia. Two patients had hypertension (including one with idiopathic hyperaldosteronism). Three patients had concurrent autoimmune thyroid diseases. There was significant clinical phenotypic overlap between PHP 1A and PHP 1B. In addition to the typical features of parathyroid hormone resistance and hypocalcemia, patients with PHP type 1 could also present with age-related serum phosphate abnormalities, hypokalemia, hypertension, autoimmune thyroid diseases, and other atypical phenotypes. Regarding genetic characteristics, 4 cases of PHP 1A exhibited maternally inherited inactivating variants in the GNAS gene. Among the 11 PHP 1B cases, 10 had methylation defects in the GNAS gene imprinting control region (including 3 familial cases and 7 sporadic cases), while the remaining 1 case had a copy number variation [20(chr20:?_44996182-62737512_?)*2 ROH], representing paternal uniparental disomy of chromosome 20q, consistent with sporadic PHP1B. In clinical practice, precise classification requires the integration of clinical phenotypes with molecular genetic findings, along with systematic evaluation and long-term follow-up.