Proopiomelanocortin (POMC) deficiency
Proopiomelanocortin deficiency, also known as POMC (pronounced POM-see) deficiency, is part of a larger group of disorders known as rare genetic disorders of obesity.
What causes POMC deficiency?
POMC deficiency can be caused by a variant variant Genetic variants may result in serious health problems or be “silent” with no negative health effects. , or change, in the POMC 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. . Usually, the POMC gene provides instructions to help run an important pathway in the brain, the melanocortin-4 receptor (MC4R) pathway MC4R pathway The MC4R pathway is one of the pathways that regulates weight and appetite in the brain. . The MC4R pathway tells us when to eat and when we are full. Variants or changes in the POMC gene can stop a part of this pathway from working and prevent this important message from being sent.
What are the key clinical features of POMC deficiency?
The main signs and symptoms of POMC deficiency include:
Severe, early-onset obesity by age 1
Excessive eating caused by insatiable hunger
Hormone level differences known as endocrine abnormalities endocrine abnormalities The endocrine system is made of organs, glands, and hormones that tell the body how to do its job. This system influences how your heart beats, how you use the food you eat, how you grow, and many other important body functions. An endocrine abnormality means that one or more parts of the system is not working the way it should.
Additional signs and symptoms
Babies with POMC deficiency are typically of average birth weight and have a standard feeding schedule. But within the first few weeks of their lives, they can develop an insatiable appetite and cry constantly to be fed. Because of these symptoms, babies with POMC deficiency may start to gain weight rapidly, with their body mass index (BMI) likely falling at or above the 95th percentile for their age. Most people with POMC deficiency also continue to experience insatiable hunger and severe obesity into adult life.
Infants with POMC deficiency may also have a condition known as adrenal insufficiency, which causes low levels of adrenocorticotropic hormone (ACTH) acth ACTH is a hormone produced by the small adrenal glands located on the top of the kidneys. Reduced ACTH levels cause a condition called adrenal insufficiency. In individuals with POMC deficiency, adrenal insufficiency often results in extended periods of extremely low blood sugar (hypoglycemia). . Low levels of ACTH can lead to very low blood sugar and even seizures and can be life-threatening without medical intervention.
Some people, but not all, may also have:
- Mildly low thyroid levels (hypothyroidism hypothyroidism A condition caused when the thyroid doesn’t make enough of certain hormones. Symptoms of hypothyroidism include fatigue, constipation, poor temperature regulation, and thinning hair. )
- Adolescent-onset growth hormone (GH) deficiency Adolescent-onset growth hormone (GH) deficiency Growth hormone deficiency is a condition where the body does not have enough of the hormone that helps us grow. Many factors, including genetics, can cause this condition. When it begins in adolescence, it is known as adolescent-onset growth hormone deficiency.
- Delayed puberty in adolescence caused by hormonal imbalances (hypogonadotropic hypogonadism hypogonadotropic hypogonadism A rare disorder of delayed puberty that happens when levels of gonadotropin hormones (Gn) are too low, which leads to low levels of other key hormones like follicle-stimulating hormone (FSH) and luteinizing hormone (LH). )
- Red hair and light skin pigmentation
- Liver disease
How is POMC deficiency inherited?
POMC deficiency is inherited 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. manner. This means that someone with POMC deficiency will have two copies of the genetic variant genetic variants Changes (also known as variants) in the standard “spelling” of a gene. Gene variants can result in serious health problems or be “silent” with no negative health effects. that causes the disorder. You can only inherit an autosomal recessive disorder if both parents are “carriers 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. ” for that disorder, meaning that they both carry one copy with the genetic variant and one copy without it.
In very rare cases, someone who is a carrier for POMC deficiency (meaning they have just one disease-causing variant) may develop some of the symptoms of the disorder. This is known as “POMC heterozygous deficiency.”
Proprotein convertase subtilisin/kexin type 1 (PCSK1)
POMC deficiency can also be caused by a variant in the PCSK1 gene, which is also located on the MC4R pathway. People with this variant may experience symptoms like insatiable hunger, malabsorptive diarrhea, and endocrine abnormalities.
How is POMC deficiency diagnosed?
If a diagnosis of POMC deficiency is suspected by your doctor based on clinical signs and symptoms, a special genetic blood test can be ordered to help confirm the diagnosis by genetic testing.