Endocrine Abstracts

Background: Pseudopseudohypoparathyroidism is a rare genetic disorder caused by heterozygous paternally inherited inactivating mutations in the GNAS gene, leading to the skeletal phenotype of Albright Hereditary Osteodystrophy (AHO), but without the hormone resistance. Our PPHP case had normal stature and shortened metacarpals on presentation along with an elevated parathyroid hormone (PTH) thus sharing features with PHP1a/c and PHP1b.

Case Presentation: An 11-year-old female presented to the maxillofacial team with a peripheral ossifying fibroma of her hard palate which required excision. There was no personal or family history of bone disorders or fractures. Dietary history revealed minimal dairy intake. On examination, she had no dysmorphic features, puberty was established, she had short 3rd–5th metacarpals and partial syndactyly of the 2nd and 3rd toes. Her height was on the 25th centile, but with a recent trajectory indicating a final height below the 0.4th centile. Baseline bloods indicated elevated PTH levels of 34.9 pmol/l (1.3-9.3), low Vitamin D (23 nmol/l) and normal calcium, phosphate, ALP and thyroid function. LH 5.1 IU/l, FSH 8.9 IU/l and oestradiol 270 pmol/l. She was commenced on vitamin D treatment and an increase in dietary calcium was advised. The bone age was advanced by two years and showed short and broad 3rd to 5th metacarpals. A skeletal survey confirmed brachydactyly, cone-shaped epiphyses, osteopenia, square iliac bones, and mild vertebral endplate changes. The diagnosis was suggestive of pseudohypoparathyroidism. Genetic testing confirmed a GNAS-related disorder consistent with pseudopseudohypoparathyroidism.

Conclusion: At presentation, this girl exhibited features overlapping with both AHO and PHP1b. However, the elevated PTH was due to secondary hyperparathyroidism caused by co-existing Vitamin D deficiency and low dietary calcium, rather than true PTH resistance. The normal stature was due to well established puberty with the final height expected to be very short. This case highlights the importance of careful clinical, pubertal, biochemical and dietary assessment when considering the differential diagnosis of GNAS-related disorders. Genetic confirmation is key as it facilitates appropriate counselling and family planning. Given the complex imprinting pattern of the GNAS gene, her offspring are at risk of inheriting PHP1a.