pharmacoligical treatment of a pateint with lifelong obesity and heterozygous complete loss of function melonocortin 4 receptor mutation

Abstract

The heterozygous melanocortin 4 receptor (MC4R) mutation is considered a primary factor in 2% to 4% of patients with obesity. Pharmacological treatment, including long-term, is emerging as a new standard for obese patients; however, there are no published reports on treatment outcomes in obese patients with documented MC4R mutations. Weight loss occurs with diet restriction or bariatric surgery and is often followed by a weight regain phase in patients with or without the MC4R mutation, indicating the need for an alternative approach to weight loss such as pharmacological treatment.This case study describes a 48-year-old woman who experienced lifelong obesity and a history of dieting that started in childhood with episodes of weight loss followed by weight gain. Her highest weight was 320 pounds in 2007. Her family's medical history included diabetes, prediabetes, and obesity. She presented to the clinic in January 2013 weighing 286.2 pounds with at-risk cardiovascular and cardiometabolic profiles. Treatment was initiated to control insulin resistance and metabolic syndrome, lower cholesterol and triglycerides, and manage hypothyroidism. Weight-loss treatment also began with a combination of bupropion and naltrexone or carbonic anhydrase inhibitors and naltrexone. Her on-treatment nutrition included eating from all food groups without counting calories or excessive exercise. In late 2014, she tested positive for a heterozygous complete loss-of-function MC4R gene mutation and weighed 213 pounds. The patient's lowest weight while on treatment was 166 pounds in August 2015. By November 2016, after experiencing partial weight regain, her weight had been stable for 6 months at approximately 198 pounds,a 30% reduction in weight from 2013.Pharmacological treatment is emerging as a recommended approach to weight loss. This case is an example of how, despite partial weight regain after weight loss, targeted pharmacological treatment can improve long-term outcomes including in patients with the MC4R complete loss-of-function mutation.