Leptin Receptor (LEPR) deficiency
Leptin receptor deficiency, also known as LEPR (pronounced LEP-ar) deficiency, is part of a larger group of disorders known as rare genetic disorders of obesity.
What causes LEPR deficiency?
Leptin is a hormone hormone Chemical messengers made in the endocrine glands that control body functions. that is produced by the body’s fat cells. The leptin hormone tells our brain when we have enough fat stored that we don’t need to eat, and that we can burn calories at a usual rate. The LEPR 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. provides the body’s instructions for making a specific protein called the leptin receptor leptin receptor An important receptor that helps the body regulate weight. The hormone leptin docks or attaches to the leptin receptor, much like a docking station. . This important receptor helps the body regulate weight.
When there is a change or variant variant Genetic variants may result in serious health problems or be “silent” with no negative health effects. in the LEPR gene, the leptin receptor cannot function correctly, and leptin cannot attach to the receptor. When the leptin does not attach to the receptor, your brain does not get the message that it is full. Without the correct signal signal Chemicals and proteins that the body and brain use to communicate and direct processes in the body. , your body can start to think that it is starving.
What are the key clinical features of LEPR deficiency?
The main signs and symptoms of LEPR deficiency include:
- Insatiable hunger
- Severe, early-onset obesity
- Delayed puberty in adolescence (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). )
LEPR deficiency, like many rare disorders of obesity, begins at a very young age. Babies are normal weight at birth but show signs of constant and insatiable hunger followed by severe, early-onset rapid weight gain within their first few weeks of life. In early childhood, abnormal eating and food-seeking behaviors develop, such as fighting with other children over food, hoarding, and secretly hiding food. If food is denied, aggressive behavior is noted. Some people also develop type 2 diabetes by early adulthood.
How is LEPR deficiency inherited?
LEPR 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 LEPR 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 of your parents are “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. ” 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 LEPR deficiency (meaning they have just one disease-causing variant) may develop some of the symptoms of the disorder.
How is LEPR deficiency diagnosed?
If a diagnosis of LEPR deficiency is clinically suspected, a blood test can be ordered for genetic testing to help confirm the diagnosis.