MON-757 - When "Epilepsy" Is Hypocalcemia: Pseudohypoparathyroidism Type 1B Overshadowed by A Long-Standing Refractory Seizure Disorder

Pseudohypoparathyroidism type 1b (PHP1b) results from epigenetic defects at the GNAS locus, leading to PTH resistance. Unlike type 1a, patients with PHP1b typically lack the physical characteristics of Albright’s Hereditary Osteodystrophy (AHO), making clinical recognition challenging. The present case describes the clinical trajectory of a patient misdiagnosed with a seizure disorder for 50 years, highlighting how the absence of somatic features can lead to significant diagnostic delays and severe complications.

A 51-year-old female presented to the endocrinology outpatient clinic for evaluation of a suspected metabolic bone disease. Her medical history was notable for "seizures" commencing at 8 months of age, historically managed as epilepsy. At age 14, extensive cerebral calcifications were documented but attributed to idiopathic causes. She also carried a diagnosis of hypothyroidism from age 25 (managed with Levothyroxine 100 mcg) and had a history of fragility fractures (right wrist/left hip arthroplasty). Despite chronic symptoms, metabolic evaluation was delayed until the fifth decade of life. Physical examination revealed no phenotypical signs of AHO, and no radiological abnormalities on hand X-rays. Biochemical workup demonstrated severe PTH resistance: PTH was markedly elevated at 894.4 pg/mL, accompanied by hypocalcemia mg/dL and hyperphosphatemia 5 mg/dL. 25-OH Vitamin D levels were 50.50 ng/mL. Renal and thyroid function was preserved. The "seizures" were reinterpreted as hypocalcemic tetany, while the extensive intracranial calcifications were attributed to long-standing hyperphosphatemia. Treatment was optimized with Calcitriol (0.25 mcg BID), high-dose Calcium Citrate, and Sevelamer to control the calcium-phosphorus product (goal < 55 mg/dL) and prevent further soft tissue calcification.

The importance of excluding metabolic etiologies in patients with refractory epilepsy and intracranial is highlighted in the present case. In retrospective, the presence of basal ganglia calcifications at age 14 was a missed red flag for chronic hyperphosphatemia. Unlike PHP1a, PHP1b typically lacks the AHO phenotype (brachydactyly, obesity), making clinical recognition difficult without biochemical screening. Hypothyroidism suggests a potential multi-hormone resistance or coincidental autoimmunity, often seen in GNAS-related disorders.

Pseudohypoparathyroidism 1b should be considered in the differential diagnosis of any patient presenting with seizures and intracranial calcifications, regardless of age. Early recognition prevents decades of mismanagement and catastrophic sequelae such as extensive brain mineralization and unnecessary antiepileptic drug exposure. The use of phosphate binders is crucial in adult PHP patients to allow for adequate calcium supplementation without precipitating further ectopic calcification.

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