What are POMC, PCSK1, and LEPR deficiency?
POMC, PCSK1, and LEPR deficiency are all rare genetic diseases of obesity
POMC stands for proopiomelanocortin
PCSK1 stands for proprotein convertase subtilisin/kexin type 1
LEPR stands for leptin receptor
These conditions occur when both copies of the relevant gene (one inherited from the mother and one from the father) have a specific change, or variant. These genetic variants affect how the brain controls feelings of hunger, which leads to weight gain.
POMC, PCSK1, and LEPR deficiency have a wide range of symptoms that can impact many systems in the body
Brain
- Insatiable hunger (hyperphagia) and resulting obesity
Endocrine
- Low levels of the hormone that manages blood sugar and metabolism (adrenal insufficiency)
Other symptoms may include:
- Endocrine: Low thyroid levels (hypothyroidism), adolescent-onset growth hormone deficiency, low blood sugar (hypoglycemia)
- Reproductive: Delayed puberty caused by hormonal imbalances (hypogonadotropic hypogonadism)
- Immune: Red hair and light skin pigmentation
- Hepatic: Liver failure
Brain
- Insatiable hunger (hyperphagia) and resulting obesity
Digestive
- Upset stomach, including diarrhea within the first weeks of life
Kidneys
- Build up of acid in the body
- Excessive thirst
Endocrine
- Diabetes
- High insulin levels in the blood
- Low blood sugar (hypoglycemia)
Other symptoms may include:
- Endocrine: Low thyroid levels (hypothyroidism), decreased cortisol production
- Other: Failure to thrive in infancy
Brain
- Insatiable hunger (hyperphagia) and resulting obesity
Endocrine
- High insulin levels in the blood
Reproductive
- Delayed puberty caused by hormonal imbalances (hypogonadotropic hypogonadism)
Other symptoms may include:
- Endocrine: Diabetes
What is hyperphagia?
Appetite control can be a struggle for many people living with obesity, but with POMC, PCSK1, and LEPR deficiency, insatiable hunger (hyperphagia) is different
In people living with POMC, PCSK1, or LEPR deficiency, insatiable hunger and obesity are caused by a genetic change that makes it difficult for the brain's hunger signaling pathway to help you feel full. That's why medicine like IMCIVREE can help
It felt as if I could only think about food, and when I wanted to eat something, I searched until I found it.
— Person who is living with POMC deficiency
What I recall is this addiction-like desire for food and this constant preoccupation with it. It’s more than the physical feeling of hunger. It also plays on a mental level.
— Person who is living with POMC deficiency
When I would start eating something, I’d eat the whole thing. No matter what sort of package it was I’d always eat the whole thing. I also ate it at an enormous tempo. It was really terrible.
— Person who is living with LEPR deficiency
In people living with POMC, PCSK1, or LEPR deficiency, insatiable hunger and obesity are caused by a genetic change that makes it difficult for the brain's hunger signaling pathway to help you feel full. That's why medicine like IMCIVREE can help
How does my brain control hunger?
The key area of the brain that communicates being hungry or full is known as the hypothalamus.
Think of the hypothalamus as a neighborhood within the brain.
In this neighborhood, there are roads that allow trucks to travel to and from the brain. One road is called the melanocortin-4 receptor, or MC4R, pathway.
The trucks on this road deliver messages between the body and the brain. These messages control hunger.
On this road, there is a traffic light, or a POMC, PCSK1, or LEPR gene, that helps guide the trucks to deliver their messages.
What causes hunger and obesity in POMC, PCSK1, and LEPR deficiency?
In people living with POMC, PCSK1, or LEPR deficiency, the signals that turn hunger “off” don’t work correctly in the brain
When the POMC, PCSK1, or LEPR gene is normal, without a variant (or change), the traffic light works correctly. The road (MC4R pathway) is open, and the trucks can deliver messages to the brain that the body is satisfied and doesn't need more food.
In people living with POMC, PCSK1, or LEPR deficiency, the traffic light is broken due to the change in the relevant gene
When the POMC, PCSK1, or LEPR gene has a variant (or change), the traffic light is broken, which causes a traffic jam. The trucks can no longer travel along the road (MC4R pathway) to properly deliver messages to the brain that the body is satisfied and doesn’t need more food. Instead, the body believes that it’s still hungry.
IMCIVREE is designed to target an impaired MC4R pathway in the brain, a root cause of hunger and obesity in people living with POMC, PCSK1, or LEPR deficiency
