Late-onset atypical pseudohypoparathyroidism type 1A with intracranial calcification and epilepsy associated with a novel GNAS variant: a case report

Abstract

Pseudohypoparathyroidism (PHP) type 1A is a rare inherited disorder characterized by resistance to parathyroid hormone and, typically, features of Albright hereditary osteodystrophy. We report a late-onset case in a 59-year-old woman who presented with cognitive decline, behavioral and psychiatric symptoms, gait instability, and seizure-like episodes. Laboratory tests showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone levels. Brain imaging revealed symmetrical calcifications in the bilateral basal ganglia, thalami, and periventricular regions, while electroencephalography showed epileptiform discharges. Genetic testing identified a heterozygous missense variant in GNAS, c.285C>G: p.Ser95Arg, which has not been previously reported. Based on the clinical manifestations, biochemical abnormalities, neuroimaging findings, and genetic results, the patient was diagnosed with late-onset atypical PHP type 1A. After treatment with calcium supplementation, calcitriol, and levetiracetam, no further seizures occurred, and serum calcium returned to the normal range, although cognitive improvement was limited. This case suggests that calcium-phosphate metabolism and parathyroid hormone levels should be assessed in adults presenting with symmetrical intracranial calcifications, seizures, or cognitive impairment. Genetic testing may further support early diagnosis and help reduce misdiagnosis.