About growth hormone receptor deficiency

What is growth hormone receptor deficiency?

Growth hormone insensitivity (GHI) is a group of extremely rare genetic disorders in which the body is unable to use the growth hormone that it produces. GHI can be caused by mutations in the growth hormone receptor (GHR) gene or mutations in genes involved in the action pathway within the cell after the growth hormone binds to its receptor, preventing the production of insulin-like growth factor (IGF-1), the substance responsible for the growth effects of growth hormone. Even more rarely, children with GH gene deletion who have been treated with recombinant GH develop antibodies that block GH binding to its receptor. Affected children fail to grow normally.

Children with GHRD who are treated with IGF-1 before puberty have improved growth, but, unlike children with GH deficiency given recombinant GH treatment, they do not have normal growth restored. Treatment for these conditions is only effective while the growing bones are still open, i.e. before the completion of adolescence. IGF-I insensitivity due to IGF-I receptor mutation mimics GHI, but results in less severe growth deficiency and is somewhat responsive to treatment with recombinant GH.

GHI is characterized by short stature and delayed bone age, as well as normal or high levels of circulating GH. Other common symptoms are delayed onset of puberty, prominent forehead, low blood sugar and obesity in adulthood. Except for an extremely rare form of GHI, where the gene for IGF-I is defective, brain development is normal, apparently because IGF-I can be made during fetal life without GH stimulation in the other conditions. Some, but definitely not all, patients with the less rare condition of IGF-I receptor deficiency may have mild intellectual impairment.

Laron and colleagues in Israel, first reported the condition in 1966, based on observations that began in 1958, and have continued to the present. The molecular basis for the syndrome he described, genetic mutation of the GHR in some of the Israeli patients was initially described in 1989, and since then over 40 different mutations of this protein have been identified by many investigators. The other genetic defects in the action pathway of GH after its binding to the GHR and associated with varying effects of IGF-I deficiency have been described in the past 15 years.

What are the symptoms for growth hormone receptor deficiency?

Delayed bone age symptom was found in the growth hormone receptor deficiency condition

Children with GHD are shorter than their peers and have younger-looking, rounder faces. They may also have “baby fat” around the abdomen, even though their body proportions are average.

If GHD develops later in a child’s life, such as from a brain injury or tumor, its main symptom is delayed puberty. In some instances, sexual development is halted.

Many teens with GHD experience low self-esteem due to developmental delays, such as Short stature or a slow rate of maturing. For example, young women may not develop breasts and young men’s voices may not change at the same rate as their peers.

Reduced bone strength is another symptom of AGHD. This may lead to more frequent fractures, especially in older adults.

People with low growth hormone levels may feel tired and lack stamina. They may experience sensitivity to hot or cold temperatures.

Those with GHD may experience certain psychological effects, including:

  • depression
  • lack of concentration
  • poor memory
  • bouts of Anxiety or emotional distress

Adults with AGHD typically have high levels of fat in the blood and high cholesterol. This isn’t due to poor diet, but rather to changes in the body’s metabolism caused by low levels of growth hormone. Adults with AGHD are at greater risk for diabetes and heart disease.

What are the causes for growth hormone receptor deficiency?

GHD that isn’t present at birth may be caused by a tumor in the brain. These tumors are normally located at the site of the pituitary gland or the nearby hypothalamus region of the brain.

In children and adults, serious head injuries, infections, and radiation treatments can also cause GHD. This is called acquired growth hormone deficiency (AGHD).

Most cases of GHD are idiopathic, meaning that no cause has yet been found.

What are the treatments for growth hormone receptor deficiency?

Since the mid-1980s, synthetic growth hormones have been used with great success to treat children and adults. Before synthetic growth hormones, natural growth hormones from cadavers were used for treatment.

Growth hormone is given by injection, typically into the body’s fatty tissues, such as the back of the arms, thighs, or buttocks. It’s most effective as a daily treatment.

Side effects are generally minor, but may include:

  • redness at the injection site
  • headaches
  • hip pain
  • curving of the spine (scoliosis)

In rare cases, long-term growth hormone injections may contribute to the development of diabetes, especially in people with a family history of that disease

What are the risk factors for growth hormone receptor deficiency?

A series of exceedingly rare genetic abnormalities known as growth hormone receptor deficiency prevents the body from using the growth hormone it produces. Growth hormone receptor deficiency can result from mutations in the growth hormone receptor (GHR) gene or in genes involved in the cell's action pathway after the growth hormone binds to its receptor. These mutations prevent the production of insulin-like growth factor (IGF-1), which is what gives growth hormone its growth-promoting effects. Even less frequently, recombinant GH-treated children with GH gene deletions produce antibodies that prevent GH from attaching to its receptor. Children who are affected don't develop normally.

Risk factors for growth hormone receptor deficiency

1. Growth hormone receptor deficiency is caused by an autosomal recessive genetic illness and is brought on by mutations in the growth hormone receptor deficiency gene or in the STAT5b, IGF-1, and IGFALS genes that are involved in the cell's intracellular signaling pathway when GH attaches to its receptor. The risk factors associated with growth hormone receptor deficiency are-

2. When a person receives two copies of an atypical gene for the same trait, one from each parent, recessive genetic diseases result. An individual will be a carrier for the condition but will not exhibit any symptoms if they inherit one normal gene and one disease gene.

3. With each pregnancy, there is a 25% chance that two carrier parents will pass the mutated gene and result in an afflicted child. With each pregnancy, there is a 50% chance that the child will carry the same gene as one of the parents. A child has a 25% chance of inheriting normal genes from both parents. Both men and women are at the same level of danger.

4. Close relatives (consanguineous) are more likely than unrelated parents to share the same defective gene, increasing the likelihood that their offspring may develop a recessive genetic condition.

Severe growth failure,Delay in tooth eruption,Hands and feet are smaller than normal,High-pitched voice,Delay in development
Development delay
Mcasermin rinfabate

Is there a cure/medications for growth hormone receptor deficiency?

Children with congenital GHD are often treated with growth hormone until they reach puberty. Often, children who have too little growth hormone in their youth will naturally begin to produce enough as they enter adulthood.

However, some remain in treatment for their entire lives. Your doctor can determine whether you need ongoing injections by monitoring hormone levels in your blood.

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