Pseudohypoparathyroidism - epidemiology, mortality and risk of complications

Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications.

Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts.

For each case, three age- (±2 years) and gender-matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1-62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene.

Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P < 0·01), infections (P < 0·01), seizures (P < 0·01) and cataract (P < 0·01), whereas their risk of renal, cardiovascular, malignant disorders and fractures was compatible with the general background population. The same tendencies were found in a subgroup analysis in cases with genetically verified PHP.

Patients with PHP have an increased risk of neuropsychiatric disorders, infections, cataract and seizures, whereas mortality among PHP patients is compatible with that in the background population.