Rare Causes of Obesity

Obesity is a multifactorial disease that is caused by various environmental, endocrine, and neurobehavioral factors.  The current prevalence of obesity is greater than 40% of the US population. Some common disorders that can contribute to weight gain include hypothyroidism, insulin resistance, and polycystic ovarian syndrome. There are also some less common causes of obesity.

There are over 90 identified rare genetic diseases that can lead to obesity including:

• Leptin Deficiency and Leptin Receptor Deficiency: two rare diseases marked by severe early hunger and rapid weight gain after normal birth weight. Leptin is a hormone that helps with satiety and these genetic mutations are both marked by significant appetite.
• Melanocortin 4 Receptor Deficiency: the most common, known genetic defect predisposing to obesity, which can either be autosomal dominant or recessive. It is often characterized by extreme hunger and childhood obesity, along with insulin resistance and increased height.
• Prader-Willi Syndrome: often caused by a loss of function in a portion of chromosome 15, which is characterized by insatiable hunger along with low muscle tone, short stature, and mild to moderate intellectual impairment.  Those with the syndrome often have fair skin, light hair, and almond shaped eyes.
• Bardet-Biedl Syndrome: an autosomal recessive disorder that is often associated with blindness, no sense of smell, and hearing loss.  

Hypothalamic Obesity: is caused by damage to hypothalamus (part of the brain involved with sleep, body temperature, and hunger regulation). The hypothalamus also makes hormones that signal the pituitary gland. The symptoms of hypothalamic obesity include intense hunger, rapid weight gain, and low metabolic rate.

Cushing Syndrome: is an endocrine disorder that has signs and symptoms of excessive cortisol. Cushing syndrome most commonly affects adults and can be caused by excessive cortisol production by the body (endogenous) or from outside the body with medication use (exogenous). Signs and symptoms include fatty hump between the shoulders, round face, dark stretch marks and central weight gain.

Lipedema: is a chronic disease of lipid metabolism with symmetrical swelling of the legs caused by increased fatty tissue distribution and storage, as well as increased growth of individual fat cells. Of note it often spares the feet and is often misdiagnosed as lymphedema.

There are many rare causes of obesity that we know about and even more that we still do not fully understand.  While there are many common causes, if you have unexplained gain especially if accompanied by intense hunger or early onset, you should discuss this with your primary care doctor or consider meeting with an obesity medicine provider.

DISCLAIMER: Sarah Smith MD is a medical doctor, but she is not your doctor, and she is not offering medical advice on this website. If you are in need of professional advice or medical care, you must seek out the services of your own doctor or health care professional.