Atypical presentation of pseudohypoparathyroidism with absence of mutations in the GNAS gene: a case report.

Background: This case report aimed to broaden the understanding of pseudohypoparathyroidism (PHP) manifestations when typical mutations in the GNAS gene are absent. The clinical, biochemical, and genetic investigations of a PHP case revealed diagnostic challenges and emphasized the importance of comprehensive genetic analysis for early diagnosis and appropriate management, as well as improved patient outcomes.

Case presentation: The case involved a 21-year-old man who has experienced recurrent limb convulsions and episodes of altered consciousness since the age of eight. Recent assessments during frequent hospitalization uncovered findings consistent with PHP, including hypocalcemia, hyperphosphatemia, elevated parathyroid hormone level, and short stature. Notably, genetic testing did not reveal mutations in the GNAS gene, which could be typically associated with PHP. Diagnostic tests revealed mild abnormalities in the electroencephalogram and multiple abnormal signals in brain magnetic resonance imaging, specifically in the caudate, lenticular, dentate, and thalamus nuclei. Cranial computed tomography scan confirmed symmetrical calcifications in the basal ganglia. Biochemical analysis revealed severely altered calcium and phosphorus metabolism. Routine endocrine and neurological evaluations yielded results within normal ranges. Genetic testing identified a novel missense mutation in the GHSR gene, which has not been reported in the database and may reasonably explain some of the patient's phenotypic features.

Conclusions: While mutations in the GNAS gene are the primary genetic markers for PHP, the presence of other genetic mutations in some cases complicates the clinical analysis. This case highlights the need for a comprehensive genetic screening approach in patients with PHP-like symptoms who do not exhibit mutations in the GNAS gene, to avoid misdiagnosis and ensure timely intervention.

Clinical trial number: Not applicable.