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 diseases of obesity.

What causes LEPR deficiency?

Leptin is a 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 provides the body’s instructions for making a specific protein called the . This important receptor helps the body regulate weight.

When there is a change or a biallelic 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 , 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 hypogonadismhypogonadotropic 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 diseases 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 recessiveAutosomal 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 variant 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 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.” 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 LEPR deficiency is suspected by your doctor based on clinical signs and symptoms, a genetic test can be ordered to help confirm a diagnosis.

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LEPTIN RECEPTOR (LEPR) DEFICIENCY

What causes LEPR deficiency?

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