Aims To highlight a rare cause of obesity in infancy and its investigations.
Methods A 3 months old girl was referred for excessive weight gain. Born at 41+6 weeks gestation, she weighed between 2nd-9th centile. At 3 months old, her weight increased to between 75th-91st centile. She had prominent physical features ie. full cheeks, truncal obesity and broad thumbs and fingers. Her karyotype was 46, XX and microarray testing for Prader Willi Syndrome was negative. Her excessive weight gain was attributed to overfeeding. At 8 months old, her weight escalated to 91st centile despite feed reduction. Also, she was short (height: 9th centile) and had global developmental delay. Patient’s mother is also short (height: 149.8 cm) with broad hands and feet and had cutaneous calcification. Clinical geneticist reviewed patient and suspected Albright Hereditary Osteodystrophy (AHO). Specific genetic testing confirmed AHO (c. 840–2A >g mutation in GNAS1) at age 1. Patient’s mother also has AHO as per genetic testing. Shortly after diagnosis, patient developed cutaneous calcifications.
ResultsGlucagon test at 14 months old showed normal growth hormone (Peak: 8.60ug/L) and cortisol (Peak: 716 nmol/L) levels (Table 1).
Levothyroxine was started at age 1.
Conclusion AHO is a constellation of clinical manifestations ie. central obesity, short stature, rounded face, brachydactyly, subcutaneous ossifications and mental retardation. These features are associated with resistance to PTH and other hormones ie. TSH, Growth Hormone Releasing Hormone (GHRH) and gonadotropins.
This case highlights AHO as an important but rare diagnosis to consider in infants presenting with obesity. There are associated diagnostic challenges as AHO clinical features are not obvious at birth or shortly after and may be very heterogeneous later. Furthermore, in children <1 year old, their PTH and TSH levels usually remain normal as hormonal resistance develops over the first year of life.