ESPE Abstracts

Background: GNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein–coupled receptor (GPCR) signaling. Mutations in GNAS are known to cause pseudohypoparathyroidism (PHP). Children with this condition are overweight, have learning difficulties, are often short and have skeletal changes and hormone resistance.

Case report: We-herein-report a 6-month-old male infant born to non-consanguineous parents. He presented with rapid weight gain noticed at 2 months of age (5.5 kg) and hyperphagia demanding breast-feeding every half an hour. He gained almost 5 kgs over 2 months. He was born at term with birth weight 2.900 kg. Solid food was introduced at age 4 months. His mother was overweight, and his grandfather had type 2 DM. His development was normal for his age. By physical examination, his weight was 13 kg (+4.84 SD), height was 67 cm (-0.33 SD), and BMI 29 (>99.9th percentile, +6.6 SD) according to WHO growth charts for age and sex. His stretched penile length was 3.5 cm. His systolic blood pressure was normal, but his diastolic blood pressure was mildly elevated (92^nd percentile). He had generalized pattern of fat distribution, with no stria or acanthosis nigricans. He had macroglossia, no skeletal abnormalities. He had normal calcium level (9 mg/dl). His laboratory investigations revealed an elevated TG level, subclinical hypothyroidism (TSH 10.8 uIU/ml) and markedly raised serum leptin levels. Abdominal ultrasonography of the patient revealed fatty liver. Whole-exome sequencing identified a heterozygous GNAS mutation.

Conclusion: Pathogenic GNAS mutations may manifest with obesity alone, without hypocalcemia. So, we recommend screening children with severe early-onset obesity for GNAS deficiency. Early diagnosis would allow early detection of associations, prevent complications, and eventually improve clinical outcomes.