Rare genetic condition may offer protection from heart disease

A new study has revealed that a rare genetic condition, known as growth hormone receptor deficiency (GHRD) or Laron syndrome, may protect against cardiovascular disease.

The body’s ineffective use of its own growth hormone characterizes this condition, leading to stunted growth. Researchers have long observed in mice that this mutation significantly increases lifespan and reduces age-related diseases; however, only recently have they begun to understand its impact on human cardiovascular health.

What is Laron Syndrome?

Laron Syndrome is a rare genetic condition that primarily affects growth due to a defect in the growth hormone receptor. This defect disrupts the normal action of growth hormone, a critical regulator of growth, metabolism, and body composition.

Genetic basis

Laron Syndrome is caused by mutations in the GHR gene, which encodes the growth hormone receptor. These mutations lead to either a malformed receptor that does not function properly or to a significantly reduced number of receptors available for hormone binding.

The condition is inherited in an autosomal recessive pattern, meaning a child needs to inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Characteristics and symptoms

Individuals with Laron Syndrome are characterized by:

• Severely stunted growth, noticeable from infancy.
• Proportional body structure, despite short stature.
• Facial features that may include a prominent forehead, underdeveloped nasal bridge, and a blue tinge to the whites of the eyes.
• High levels of circulating growth hormone with low levels of IGF-1 (Insulin-like Growth Factor 1), which normally mediates many of the effects of growth hormone.

Treatment

There is no cure for Laron Syndrome, but treatment focuses on managing symptoms and improving quality of life:

• Growth hormone therapy is ineffective due to the body’s resistance to it. Instead, IGF-1 therapy has been used to promote growth in children with this condition.
• Regular monitoring and management of potential complications, such as delayed puberty and metabolic abnormalities, are recommended.

Rare genetic condition and age-related disease

Laron Syndrome continues to be an area of interest for research, not only to improve management strategies for those affected but also to understand its implications for aging and chronic diseases in the general population.

The unique characteristics of those with Laron Syndrome can provide insights into the aging process and the development of age-related diseases, offering potential pathways for developing new therapeutic approaches.

Genetic insights into Laron syndrome

Valter Longo, a professor at the USC Leonard Davis School of Gerontology, and Jaime Guevara-Aguirre, an endocrinologist at the Universidad San Francisco de Quito in Ecuador, published their findings in the journal Med on April 26, 2024.

For nearly 20 years, these researchers have been studying the health and aging impacts of the GHR mutation in Laron syndrome, predominantly found among a small population of Ecuadorians descended from exiles of the Spanish Inquisition.

Health impacts of Laron syndrome

The research focused on 51 individuals, comprising 24 with Laron syndrome and 27 of their relatives without the mutation. By conducting comprehensive assessments of cardiovascular function, damage, and risk factors both in Los Angeles and Ecuador, the team gathered significant data.

The subjects with Laron syndrome exhibited lower blood sugar levels, decreased insulin resistance, and reduced blood pressure when compared to their non-mutant relatives.

Additionally, they had smaller heart dimensions and exhibited lower carotid artery thickness despite having similar arterial stiffness.

Interestingly, even though individuals with Laron syndrome had elevated levels of LDL cholesterol, known as “bad cholesterol,” they showed a lower incidence of carotid artery atherosclerotic plaques (7% compared to 36% in the control group).

Valuable insights from the study

“These findings suggest that individuals with Laron syndrome have normal or improved levels of cardiovascular disease risk factors compared to their relatives,” stated Professor Longo, the senior author of the study.

He further noted that although the sample size is small, the human data, when combined with previous animal studies, offer valuable insights into the potential health benefits of growth hormone receptor deficiency.

The implications of this research extend beyond just understanding the rare genetic condition of Laron syndrome. They also open up possibilities for new therapeutic strategies that mimic the effects of this genetic mutation.

Potential interventions could include drugs or dietary adjustments aimed at replicating the mutation’s protective effects, thereby potentially reducing disease incidence and extending human longevity.

As this body of research grows, it continues to illuminate the complex interactions between genetics and disease, providing hope for future breakthroughs in medical science.

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