Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI-SDS-A case series.

Abstract

BACKGROUND:

The clinical phenotype of patients with monogenic obesity due to mutations in the leptin receptor (LEPR) or melanocortin 4 receptor (MC4R) gene is characterized by impaired satiety and hyperphagia, leading to extreme, sometimes life-threatening weight gain.

SUBJECTS/METHODS:

In a case series, we analysed the effect of an off-label methylphenidate (MPH) use for 1 year as an individual treatment approach on eating behaviour (Child Eating Behaviour Questionnaire [CEBQ]), appetite (visual analogue scales) and body mass index (BMI) trajectories in five patients with severe obesity due to mutations in the LEPR (n = 3) or MC4R (n = 2) gene.

RESULTS:

After 1 year use of MPH (20 mg/day divided in two to three doses), BMI (Δ BMIT0-T1x¯ : -0.7 ± 0.9 kg/m2 ), BMI standard deviation score (SDS) (Δ BMI-SDST0-T1x¯ : -0.32 ± 0.20), and %BMIP95 (Δ %BMIP95T0-T1x¯ : -6.6 ± 7.8%) decreased. BMI-SDS velocity decreased from +0.17 ± 0.22 to -0.30 ± 0.20. Appetite and CEBQ subscale scores for "food responsiveness" and "enjoyment of food" decreased. We observed adverse effects with increase in self-reported frequency of disordered sleep, nervousness, hyperactivity, and tics.

CONCLUSIONS:

The observed decrease in BMI trajectories with MPH use for one year is clinically meaningful in this group of patients, since the natural course would have been associated with a pronounced increase in BMI, leading to comorbidities and complications over time.

• Authors: Stephanie Brandt, Julia von Schnurbein, Belinda Lennerz, Katja Kohlsdorf, Heike Vollbach, Christian Denzer, Harald Bode, Johannes Hebebrand, Martin Wabitsch
• Journal: Pediatric obesity (Pediatr Obes) Vol. 15 Issue 1 Pg. e12577 (01 2020) ISSN: 2047-6310 [Electronic] England
• PMID: 31670905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.

Chemical References

• LEPR protein, human
• MC4R protein, human
• Receptor, Melanocortin, Type 4
• Receptors, Leptin
• Methylphenidate

Topics

• Adolescent
• Body Mass Index
• Child
• Female
• Humans
• Male
• Methylphenidate (pharmacology)
• Mutation
• Obesity, Morbid (genetics, psychology)
• Receptor, Melanocortin, Type 4 (deficiency, genetics)
• Receptors, Leptin (deficiency, genetics)
• Satiety Response (drug effects)