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For a rare few, hunger is overwhelming

If you or someone you know has insatiable hunger, it can feel like your brain is constantly telling your body that you’re hungry. A rare genetic disorder of obesity may be the reason that your brain can’t signal signals Chemicals and proteins that the body and brain use to communicate and direct processes in the body. to your body when it’s time to stop eating.

Can you relate to these stories?

These are the stories of people living with rare genetic disorders of obesity. Rare genetic disorders of obesity are uncommon forms of severe, early-onset obesity.

Rare genetic disorders of obesity are different because they come from an unconventional root cause: changes or variants variant A change in the standard “spelling” of a gene. Genetic variants may result in serious health problems or be “silent” with no negative health effects. in a gene gene Our body’s instruction manual that informs how our bodies grow, develop, and function. It is through our genes that traits are passed down from parent to offspring. . When it comes to rare genetic disorders of obesity, individuals often instinctively know something is unusual about their weight gain, appetite, and health, but often don’t know why or how to talk about it.

The main symptoms of rare genetic disorders of obesity are:


“From an early age I can remember being very hungry. As I got older, I started to realize that I would gain weight a lot more quickly than other people even when I ate a normal amount of food.”

BECKY | Suspected of having a rare genetic disorder of obesity

Watch this video to learn more about insatiable hunger.

Insights from 3 families living with symptoms that may be related to rare genetic disorders of obesity

Hunger is a main part of our life.

SYMPTOM 1: Insatiable hunger

And it is always on Nate's mind. It controls him. And hunger is right beside him. I want to say his best friend, but it's not; it’s his mortal enemy. Hunger is his mortal enemy.

KAREN
Mom to Nate, living with POMC deficiency, a rare genetic disorder of obesity

People think that I’m making it up sometimes, and I wish that they could get inside my body and that they could feel the physical sensations of hunger so that they would fully get how hungry I feel.

BECKY
Living with a suspected rare genetic disorder of obesity

SYMPTOM 2: Weight gain despite a restricted diet and exercise

I think there is such a stigma on obesity and it’s directly correlating with, “They must eat too much. They must sit around too much.” With individuals with these disorders, that’s just not the case. No matter how much we cut their calorie intake, no matter how much they exercise, they’re going to either continue being large or they’re going to continue gaining weight.

MOLLY
Mom to Joshua, living with a suspected rare genetic disorder of obesity

I’m gaining all this weight from what’s considered a normal amount of calories; that’s a definite sign that something’s drastically wrong and that it’s a disease state.

SYMPTOM 3: Severe obesity that starts early in life

Between the ages of 4 and 6 months, he had gained about 6 pounds. On average he had gained about a pound every week thereafter. He is the average height of a 6 year old.

And so I did a food log to see how much, and I’m like, “but this is what any child at 1 1/2 would eat.” And he was gaining 3 pounds a week.

It’s a hard job, so I had to focus on the good.

You can take steps to seek more answers about rare genetic disorders of obesity

Talk to a doctor if you or someone you know shows symptoms of rare genetic disorders of obesity

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Symptoms of a rare genetic disorder of obesity

Insatiable hunger represented by fork looped into an infinity symbol

Insatiable hunger

“He wakes up in the morning hungry. He spends all day hungry. He goes to bed hungry. He will live his whole life hungry. Hunger controls him.”

KAREN | Mom to Nate, living with POMC deficiency, a rare genetic disorder of obesity

A rare genetic disorder of obesity can affect the message that’s sent to your brain to tell you when you’ve had enough to eat. This can cause you to feel an insatiable hunger. Picture going to work, connecting with friends, spending time with family, or just relaxing after a meal — and feeling hungry during every moment.

Gaining weight while on a restricted diet and exercise represented by sneaker and scale icon

Weight gain while on a restricted diet and exercise

“No matter how much we cut their calorie intake, no matter how much they exercise they’re going to continue gaining weight; that’s just how they’re built.”

MOLLY | Mom to Joshua, suspected of having a rare genetic disorder of obesity

If you have a rare genetic disorder of obesity, it is a challenge to lose weight. It’s possible that you will still gain weight while on a restricted diet.

Severe obesity early in life represented by baby bottle icon

Severe obesity that starts early in life

“He gained six pounds between a four- and a six-month checkup. He’s now three years old, but is the height of a six-year-old and the weight of a nine- or ten-year-old.”

MOLLY | Mom to Joshua, suspected of having a rare genetic disorder of obesity

Early-onset obesity is when an infant or child begins to rapidly gain weight—often as early as a few months after birth.

Read more about the science behind rare genetic disorders of obesity

Understanding obesity

What if your brain couldn’t get the signal that your belly was full? You would never know when it was time to stop eating.

Obesity is defined as a disease of excess body fat. Most people think of obesity as something that happens to people who don’t get enough exercise or consume too many calories; however, there are rare forms of obesity caused by genetic changes (or variants) that lead to insatiable hunger.

Rare genetic disorders of obesity are caused by changes in the brain’s ability to understand when the stomach is full and when the body is storing too much fat.

The hunger and brain connection

Hunger doesn’t start in your stomach. Certain parts of your brain are in charge of controlling hunger and balancing how many calories you burn and how much you weigh.

Rare genetic disorders of obesity result from the brain's inability to understand that the stomach is full and the body is storing too much fat. When all systems are functioning properly, your brain gets the signal that you are full and tells you to stop eating.

In rare genetic disorders of obesity, specific genes are not working properly and the message to your brain that says, “You're full and it’s time to stop eating” never arrives.

Energy metabolism is how your body stays in balance

Picture a seesaw that you played on at a playground as a child. The challenge was to balance the weight to be equal on both sides so that you could hover in the air, feet dangling, not moving up or down.

Rare genetic disorders of obesity can be understood using this same seesaw imagery. Our bodies try to balance the intake of food with the burning of fuel or calories. When we are in perfect balance, like on the seesaw, weight is stable and does not move. However, when there is an imbalance in the body’s energy-balance system energy-balance system How the body balances the calories we consume and the calories we expend. An imbalance in this system can lead to weight changes. , this can lead to excess hunger and excess eating.

Many areas in the brain work together to regulate hunger, and having a working melanocortin-4 receptor (MC4R) pathway MC4R pathway The MC4R pathway is one of the pathways that regulates weight and appetite in the brain. Click here to learn more about the MC4R pathway. is extra important. When the MC4R pathway is functioning properly, it tells the brain when it’s time to stop eating. When part of the MC4R pathway is broken, the body and brain can’t communicate effectively about being full and storing fat. This is what happens in rare genetic disorders of obesity.

Melanocortin-4 receptor (MC4R) pathway

  • Weight and hunger are controlled and regulated by certain genes in the body, much like traffic signals regulate traffic on a busy street.
  • Changes or variants in genes that control weight and hunger, like the MC4R pathway, may cause severe early-onset obesity and excessive insatiable hunger.
  • There are many signals on the MC4R pathway where body functions related to eating, feeling full, and storing fat can be interrupted.

The MC4R pathway in our bodies helps us know when to eat and when we are full. It also aids in controlling the storage and use of key fuels required by the body (burning calories). Rare genetic disorders of obesity are caused by changes or variants in the genes, which interrupt the signals on the pathway directing the appetite, burning of calories, and other related processes in the body.

Here's what happens when the MC4R pathway does not work properly:

MC4R pathway that shows how the "full" signal is interrupted when you have a rare genetic disorder of obesity MC4R pathway that shows how the "full" signal is interrupted when you have a rare genetic disorder of obesity

Rare genetic disorders of obesity and how they impact the brain and body can be better understood by having a basic understanding of genetics. When doctors talk about genetics and medicine, it can seem like they’re speaking a foreign language. Our goal is to explain these key terms in a way that makes sense and helps you interpret new information as it is discovered.

Genes

Genes are our body’s instruction manual, recipe book, or blueprint, which informs how our bodies grow, develop, and function. Genes are made of deoxyribonucleic acid (DNA) and lined up on chromosomes like beads on a string. It is because of our genes that we resemble our parents, siblings, and aunts and uncles; it is also through our genes that genetic conditions are passed down through the generations.

Here are some key points you need to know about genes:

  • We have two copies of most of our genes—one copy from our mother and one from our father
  • Each gene is spelled (coded) in a specific way
  • All of us have changes or variants in some of our genes which make us unique
  • Not all gene variants are disease-causing (pathogenic)
  • Sometimes both copies of a gene need to have a disease-causing variant to cause problems; other times just one disease-causing variant will be enough to cause disease.
Two chromosomes that show the difference between inheriting two copies of a gene and inheriting one copy Two chromosomes that show the difference between inheriting two copies of a gene and inheriting one copy

Patterns of Inheritance

Genetic conditions caused by gene variants can be passed down through families in several ways. Many rare genetic disorders of obesity are passed down in an autosomal recessive autosomal recessive Autosomal recessive (AR) conditions occur when a person inherits two non-working copies of a disease-causing (pathogenic) gene variant from their parents. (AR) pattern.

Autosomal Recessive Pattern of Inheritance

We all have two copies of almost every gene in our bodies. We inherit one copy from our mother and the other copy from our father. Autosomal recessive conditions occur when a person inherits two copies of a disease-causing (pathogenic) gene variant.

Child's chance of inheriting a rare genetic disorder of obesity represented by family tree with two parents and four children Child's chance of inheriting a rare genetic disorder of obesity represented by family tree with two parents and four children

Autosomal Recessive Conditions

There are several key points to know about autosomal recessive inheritance:

  • Typically, in AR conditions, if only one copy of the gene has a disease-causing variant, the person is considered a carrier carrier In an autosomal recessive inheritance pattern, if an individual inherits one normal copy of a gene and one copy of a disease-causing variant, they are called a carrier and will generally not have any symptoms of the disease that variant causes. and will generally not have any symptoms of the disease.
  • When both parents are carriers for a disorder, each child they conceive will have:
25%

A 1 in 4 chance of having the disorder

50%

A 1 in 2 chance of being a carrier of the disorder

25%

A 1 in 4 chance of being unaffected (not having the disease or being a carrier)

Rare genetic disorders of obesity are genetic conditions caused by disease-causing or pathogenic gene variants. There are also forms of obesity that appear to “run in families” but do not follow a predictable pattern or have the same early and severe symptoms.

Two ways that you can inherit obesity from your parents are:

1

A genetic predisposition to obesity

2

A genetic variant that causes obesity

Having a genetic predisposition to obesity means that you are more likely to become obese than people with a different genetic makeup. The phrase “it runs in the family” is often used to describe a genetic predisposition to obesity and other health-related problems. But just because these conditions run in your family doesn’t mean you are destined to develop obesity. Other factors like diet, activity level, and even where you live can influence whether or not you develop obesity.

Inheriting a genetic variant that causes a rare genetic disorder of obesity is different from a genetic predisposition. If you inherit a specific gene variant, you are likely to develop obesity—no matter what you change in your environment.

Factors that can lead to obesity, including genetics, diet, medical problems, and activity level Factors that can lead to obesity, including genetics, diet, medical problems, and activity level
What are rare genetic disorders of obesity?

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