Semaglutide as a potential treatment for a child with ADCY3 mutation

Canbaz Aylin Tugba; Bahar Ozcabi; Samim Ozen; Abdullah Bereket; Belma Haliloglu

doi:10.1530/endoabs.110.EP881

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Endocrine Abstracts (2025) 110 EP881 | DOI: 10.1530/endoabs.110.EP881

ECEESPE2025 ePoster Presentations Metabolism, Nutrition and Obesity (164 abstracts)

Semaglutide as a potential treatment for a child with ADCY3 mutation

Aylin Tugba Canbaz ¹ , Bahar Ozcabi ² , Samim Ozen ³ , Abdullah Bereket ¹ & Belma Haliloglu ¹

Author affiliations

¹Marmara University School of Medicine, Department of Pediatric Endocrinology and Diabetes, Istanbul, Türkiye; ²Acibadem Atasehir Hospital, Department of Pediatric Endocrinology and Diabetes, Istanbul, Türkiye; ³Ege University School of Medicine, Department of Pediatric Endocrinology and Diabetes, Istanbul, Türkiye

JOINT1526

Aim: ADCY3 mutations, a rare cause of monogenic obesity, are associated with hyperphagia, obesity, insulin resistance, hyposmia, and intellectual disability. Although no specific treatment is approved, GLP-1 receptor agonists have shown potential benefits. Here, we present our experience with Semaglutide in a patient with an ADCY3 mutation.

Case: A 4^7/12years-old female presented with hyperphagia and excessive weight gain starting at 2 months. She was born at term with a birth weight of 3050g (−0.08 SDS), her weight increased to 6.5 kg (+2.03 SDS) at 2 months,19 kg (+6.98 SDS) at 10 months, and 34 kg (+8.42 SDS) at 2.5 years. The family had a history of consanguinity but no reported obesity. At presentation, her height was 118.5 cm (+2.59 SDS), weight 64 kg (+7.86 SDS), and BMI 45.5 (+5.70 SDS). Physical examination revealed severe acanthosis nigricans, Blount’s disease impairing ambulation, stage 2 hypertension with left ventricular hypertrophy, atypical autism, and astigmatism. Laboratory findings are summarized in Table-1. Whole Exome Sequencing identified a novel homozygous warm variant of uncertain significance in the ADCY3 gene (c.1102G>A), confirmed by segregation analysis. Due to uncontrolled hyperphagia, rapid weight gain, and severe obesity-related complications, treatment with Semaglutide was initiated at a dose of 0.125mg/week. The dose was titrated to 0.50mg/week at monthly intervals, as no adverse effects were observed. The patient’s weight stabilized after 1 month at 0.50mg/week. As hyperphagia persisted without adverse effects, the dose was increased to 1 mg/week. During the first month at this dose, she lost 4.4 kg, and her weight remained stable over the following 3 months. Her BMI-SDS improved from +5.54 SDS to +4.88 SDS at seventh month of treatment (Table-2). The patient is currently under follow-up without experiencing significant adverse effects.

Table 1. Laboratory findings
	Result	Range
Fasting-Glucose(mg/dL)	79	70–100
Insulin(µIU/ml)	34.8	2–25
Hba1c(%)	5.6	4.8-5.9
TSH(mIU/L)	2.5	0.54-4.53
Free-T4(pmol/L)	18.6	11-22.5
Total Cholesterol(mg/dL)	171	8-200
HDL(mg/dL)	56	40-60
Triglyceride(mg/dL)	70	0-150
Leptin(ng/ml)	74	12-135
AST/ALT(U/L)	43/41	7-35

Table 2. Treatment Progress and Outcomes with Semaglutide
Semaglutide Dose(mg/week)	Weight-SDS	Height-SDS	BMI(kg/m²)	BMI-SDS
Baseline(4^10/12years-old)		7.90	2.24	48.0	5.54
1st-month	0.125	8.01	2.12	49.8	5.51
2nd-month	0.25	8.14	2.01	51.2	5.44
3rd-month	0.5	7.47	2.82	44.6	5.14
6th-month	1.00	7.14	2.48	46.3	4.95
7th-month	1.00	6.96	2.40	45.6	4.88

Conclusion: GLP-1RA may be considered a potential treatment option for patients with ADCY3 mutations presenting with uncontrolled hyperphagia, excessive weight gain, and severe obesity-related complications.

Keywords: ADCY3, monogenic obesity, semaglutide