Endocrine Abstracts

Background: Pseudohypoparathyroidism type 1a (PHP1a) is a rare disorder caused by a maternally inherited mutation in the GNAS gene. PHP1a is usually diagnosed in childhood due to a distinctive phenotype that includes short stature, brachydactly, ectopic ossifications, and multi-hormone resistance. These features are associated with resistance to parathyroid hormone (PTH).

Case: We report the case of a 3.4-year-old boy who presented with a generalized tonic–clonic seizure. Investigations revealed hypocalcaemia (cCa 1.78 mmol/l, PO₄ 2.01 mmol/l, PTH 68.2 pmol/l, and vitamin D 39 nmol/l). His seizure self-terminated and he was commenced on calcium and vitamin D supplementation. He was under review from the age of seven months with excessive weight gain 12.22 kg (+3.01 SDS), 72.0 cm (+0.72 SDS). At birth he weighed 3.40 kg (25th centile) and had a solitary episode of hypoglycaemia. In view of this he was thoroughly investigated and was referred for a tertiary opinion, but still no cause found. Genetics ruled out Beckwith Weiddeman and Prader–willi syndrome. His development progressed and despite strict dietary control he continued to gain weight. At 3.4 years he weighed 25.76 kg (+4.34 SDS) with BMI 25.71 kg/m² (>99.6th centile). He had a round face with short digits, and his hand X-ray was normal, but with an advanced bone age of 4.6 years. In light of hypocalcaemia and raised PTH a diagnosis of PHP was suspected, and when discussed with the family mum revealed areas of skin calcinosis. Genetic analysis showed he was heterozygous for an insertion of eight nucleotides at cDNA position 388 (c.388_389insGGTTCATC) in the GNAS1 gene. This confirmed a diagnosis of Albright’s hereditary osteodystrophy (AHO); PHP1a.

Conclusion: Although, a rare presentation Albrights should be suspected in early-onset obesity. Appropriate management ensures regulation of plasma calcium and other factors such as bone mass and TSH resistance. Follow-up should be comprehensive given the manifestations of the disease associated with being overweight.