Endocrine Abstracts

JOINT965

Introduction: POMC deficiency is an extremely rare autosomal recessive disorder caused by biallelic loss-of-function variants in the POMC gene. It is characterized by 3 major features: adrenal insufficiency, obesity due to hyperphagia, and red hair. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, was recently approved as a treatment for reducing hunger and weight in patients with POMC deficiency. Here, we describe the results of one year of treatment with setmelanotide in 2 patients with POMC deficiency.

Method: Two unrelated patients with hypoglycemia during their first days of life, recurring episodes of hypoglycemia later in their first year of life, as well as pale skin and red hair, were suspected to have POMC deficiency. Hormonal evaluation revealed low levels of ACTH, cortisol, and secondary subclinical hypothyroidism. POMC deficiency was confirmed by DNA analysis: a homozygous variant chr2:25391366C>T (hg19) at the splice donor site of intron 1 was detected, and setmelanotide treatment was started.

Results: The patients, a girl aged 9 years, with height SDS 2.9 and BMI SDS 4.0, and a boy aged 8 years with height SDS 3.8 and BMI SDS 4.4, started setmelanotide treatment at 0.5 mg/day. One week later, the dose was increased to 1 mg/day and showed a sharp decrease in appetite on the next day. For the girl, the dose was increased to 1.5 mg/day at Week 28, which was the same dose after one year of treatment. During this period, her BMI SDS decreased from 4.0 to 2.3. For the boy, the dose was increased to 1.5 mg/day at Week 10 and at Week 30 to a further, final, dose of 2 mg/day. After 10 months of treatment, BMI SDS decreased from 4.4 to 3.0 and stayed stable for the two months thereafter. Both patients tolerated the treatment well. They did require increasing doses of glucocorticoids due to hypoglycemia and reported hyperpigmentation of the skin.

Conclusion: Setmelanotide treatment in these patients with POMC deficiency was safe and effective, with a decrease in BMI SDS of 42.5% and 31.8% after one year, respectively. This indicates that setmelanotide can support patients and their families in leading a more normal and active life and help to prevent the development of severe complications caused by obesity.