SAT-684 Setmelanotide Treatment Of The Child With Morbid Obesity Secondary To A Combination Of Magel2 And Bbs19 (ift27) Genes Dramatically Improved Morbid Obesity, Liver Function, Hyperlipidemia, And Prediabetes

Abstract Disclosure: B. Labib: None. L. Musmanno: None. A. Khattab: None. S.B. Ten: None. Introduction: Setmelanotide is the first and only FDA-approved treatment for BBS. It activates MCR4 receptors in the hypothalamus, decreasing appetite and increasing energy expenditure. DAYBREAK Stage 1 clinical trial identified that Magel 2 gene responded to Setmelanotide with more than 5 % reduction in BMI on week 16. Case presentation: 12 yrs old boy presented with morbid obesity BMI 32.87 kg/m2 (Z=2.3), developmental delay, autism spectrum disorder, dyslipidemia, sleep apnea, hypotonia, prediabetes Hb A1c 5.9.He was born after a normal pregnancy, FT with BW 6 lbs 10 oz. Mother had morbid obesity, more than 300 lbs, neuropathy.A genetic test at Prevention Genetics revealed IFT27 and MAGEL 2 heterozygous polymorphism. In the IFT27 gene, a sequence variant defined as c.296G_A was identified; this variant is a loss-of-function allele, and is likely pathogenic. Biallelic variants in IFT27 are associated with Bardet-Biedl syndrome (OMIM #615996). Also, heterozygous changes in the MAGEL2 gene for a sequence variant were defined as c.886G_C, which is predicted to result in the amino acid substitution p.Ala296Pro. This variant has not been reported in the literature. Paternally inherited or de novo pathogenic variants on the MAGEL2 paternal allele cause autosomal dominant Schaaf-Yang syndrome (OMIM 615547). Clinical features of the patient included:He had poor muscle tone at birth with feeding problems and failure to thrive in infancy, followed by progressive weight gain and polyphagia from 9 months of age. Morbid obesity is complicated by elevated triglycerides, LDL, low HDL, Sleep apnea, prediabetes, Hb A1c 5.9.He has a learning disability, developmental delay, difficulty with social interaction skills, in a special class, and has speech therapy at school.He has Central auditory processing disorder.Abdominal sonogram was normal, kidney sonogram was normal, no cysts.MRI of the brain and pituitary was normal. After 7 months of therapy with Setmelanotide BMI decreased 15 % from 32.87 (Z = 2.24) to 27.8 kg/m2 (Z = 1.93). Hb A1c from 5.9 to 5.7, AST 28 to 23, ALT 33 to- 25, HDL 38 to 40, TG 142 to 126. Conclusion: Setmelanotide therapy was effective in the case of BBS 19 (IFT27) and MAGEL 2 heterozygous polymorphism.. BMI decreased 15 %, and Hb A1c went from 5.9 to 5.7. The child tolerated therapy well. Only mild skin pigmentation was noted. Presentation: Saturday, July 12, 2025