Introduction: Albrights Hereditary Osteodystrophy (AHO, Pseudohypoparathyroidism type 1a) is inherited in an autosomal dominant manner. End-organ resistance is seen, primarily affecting parathyroid hormone (PTH) and thyroid hormones (TSH). The manifestation of hormone resistance, in particular resistance to PTH, depends on whether the mutated allele is inherited maternally or paternally.
Cases: A 4 year old male child was incidentally found to have hypocalcaemia (Serum Calcium: 1.72 mmol/l) with normal ALP as part of screening blood tests for speech difficulties. Further investigations identified raised PTH (72.2 pmol/l) with normal Vitamin D (42 nmol/l) and normal Urine Ca:Creatinine ratio. He was noted to be short compared to parents heights, had short stubby fingers, small, hard subcutaneous swellings on the right wrist and chest wall suggestive of subcutaneous calcification. Wrist X-ray revealed short 4th and 5th metacarpals and soft tissue calcification over the volar aspect of the 1st MCP joint. Diagnosis of AHO was considered which was confirmed by Genetics test (GNAS Gene changes). He was commenced on One Alpha and oral Calcium. His 7 year old sister had undergone operation in infancy for removal of a swelling on the chest wall which had revealed calcification on biopsy. She underwent assessment and was noted to be short, had short stubby fingers and firm, small, subcutaneous swellings on her right heel, wrist and thigh. Blood tests confirmed hypocalcaemia (Serum Calcium: 1.62 mmol/l), raised PTH (91.4 pmol/l) with normal Vitamin D and urine Ca:Creatinine ratio. Diagnosis of AHO confirmed and treatment commenced. Family were referred to the genetics team who confirmed several family members on maternal side of the family had AHO (mother, mothers twin sister, maternal uncle and maternal grandfather) with no evidence of hormone resistance.
Conclusion: Full expression of the gene (AHO + hormone resistance) occurs in maternally inherited cases (the two children) and partial expression (AHO alone) occurs when the gene is inherited from the father (mother and her siblings inherited from their father). This differential effect of the gene suggests the involvement of genomic imprinting of the GNAS1 gene in the expression of this disorder.
22 - 24 Nov 2017
British Society for Paediatric Endocrinology and Diabetes