Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies

Mainieri, Francesca; La Bella, Saverio; Rinaldi, Marta; Chiarelli, Francesco

doi:10.1007/s00431-024-05427-4

Eur J Pediatr

2024

DOI: 10.1007/s00431-024-05427-4

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Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies

Francesca Mainieri,

Saverio La Bella,

Marta Rinaldi

et al.

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2024

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Cited by 4 publications

References 74 publications

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Precision medicine to identify, prevent, and treat pediatric obesity

Tillman,

Mertami

2024

Pharmacotherapy

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Pediatric obesity is a growing health concern that has many secondary adverse health implications. Personalized medicine is a tool that can be used to optimize diagnosis and treatments of many diseases. In this review, we will focus on three areas related to the genetics of pediatric obesity: (i) genetic causes predisposing to pediatric obesity, (ii) pharmacogenomics that may predict weight gain associated with pharmacotherapy, and (iii) pharmacogenomics of anti‐obesity pharmacotherapy. This narrative review evaluates genetic cause of pediatric obesity and how genetic findings can be used to optimize pharmacotherapy to minimize weight gain and optimize obesity treatment in pediatric patients. Pediatric obesity has many genetic causes including genomic obesity syndromes and monogenic obesity disorders. Several genetic etiologies of obesity have current or emerging targeted genetic therapies. Pharmacogenomic (PGx) targets associated with pharmacotherapy‐induced weight gain have been identified for antipsychotic, antiepileptic, antidepressant therapies, and steroids, yet to date no clinical guidelines exist for application use of PGx to tailor pharmacotherapy to avoid weight gain. As legislation evolves for genetic testing coverage and technology advances, this will decrease cost and expand access to genetic testing. This will result in identification of potential genetic causes of obesity and genes that predispose to pharmacotherapy‐induced weight gain. Advances in precision medicine can ultimately lead to development of clinical practice guidelines on how to apply genetic findings to optimize pharmacotherapy to treat genetic targets of obesity and avoid weight gain as an adverse event associated with pharmacotherapy.

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Precision medicine to identify, prevent, and treat pediatric obesity

Tillman,

Mertami

2024

Pharmacotherapy

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Use of glucagon-like-peptide 1 receptor agonist in the treatment of childhood obesity

Kavarian,

Mosher,

Abu El Haija

2024

Current Opinion in Pediatrics

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Purpose of review Pediatric obesity is a growing epidemic. Lifestyle modifications remain central to obesity treatment, however pharmacologic options have gained traction, particularly glucagon-like peptide-1 receptor agonists (GLP-1RA). This review aims to summarize evidence on the use of GLP-1RAs in the management of pediatric obesity, physiological mechanisms of action of GLP-1RAs and their role in appetite regulation and glucose homeostasis and address the challenges and special considerations surrounding GLP-1RA use. Recent findings Recent studies have highlighted the efficacy of GLP-1RAs, such as exenatide, liraglutide, and semaglutide, in promoting weight loss and improving metabolic parameters in children and adolescents. GLP-1RA's efficacy extends beyond glycemic control to include weight loss mechanisms such as delayed gastric emptying (gastroparesis), and appetite suppression. Semaglutide, the newest GLP-1RA, holds potential for substantial weight loss in adolescents and demonstrates a similar safety and efficacy as seen in adults. Summary GLP-1RAs may offer a promising adjunct therapy for pediatric obesity, particularly in cases where lifestyle interventions alone are insufficient. However, further research is needed to elucidate long-term safety and efficacy outcomes and to address potential disparities in access to care. Overall, this review highlights the relevance and timeliness of incorporating GLP-1RAs into the comprehensive management of pediatric obesity.

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Testing for Endothelial Dysfunction in Children with Rare Genetic Variants of Obesity

Farhat,

Chin

2024

Endocrines

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Background: Endothelial dysfunction (ED), an early indicator of atherosclerosis, is a well-established predictor of cardiovascular disease. This study investigates ED in children with rare genetic variants linked to obesity and explores the prevalence of these variants in pediatric obesity. Methods: Under an IRB-approved protocol, 54 pediatric patients with severe obesity (BMI ≥ 97%) were screened using the Rhythm® Genetics Test panel between 2021 and 2024 through the Uncovering Rare Obesity® program. This clinically approved buccal test targets 79 genes and one chromosomal region. ED was measured using EndoPAT® (Itamar Medical Ltd by Zoll US based company) in 24 of these patients with related gene variants and compared to controls. Results: Genetic screening: Among the 54 patients screened, 42 (78%) had positive genetic variants, including 18 males and 24 females. The most common variants were PCNT (n = 9), BBS (n = 9), SEMA3 (n = 8), ALMS1 (n = 6), SDCCAG8 (n = 5) and MC4R (n = 5). Endothelial dysfunction: Included 21 subjects with a mean age of 12 years and a mean BMI of 33.31 kg/m². The mean RHI for patients with the PCNT variant was significantly higher (1.34, p = 0.02) compared to controls, but no significant differences were observed for other variants, including BBS, ALMS1, and SH2B1. Conclusions: In this small pilot study, no significant difference in ED was found between children with or without genetic variants, except for PCNT, which showed a higher RHI. Targeted genetic screening revealed 78% with identified pathogenic variants like MC4R, which can clinically guide therapy. Further research is needed to investigate ED in children with obesity variants.

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Rare genetic forms of obesity in childhood and adolescence: A narrative review of the main treatment options with a focus on innovative pharmacological therapies

Cited by 4 publications

References 74 publications

Precision medicine to identify, prevent, and treat pediatric obesity

Precision medicine to identify, prevent, and treat pediatric obesity

Use of glucagon-like-peptide 1 receptor agonist in the treatment of childhood obesity

Testing for Endothelial Dysfunction in Children with Rare Genetic Variants of Obesity

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