Type A insulin resistance syndrome
Type A insulin resistance syndrome is a rare genetic disorder characterized by severe insulin resistance, often leading to diabetes mellitus and specific hormonal abnormalities in females.
Overview
This syndrome is part of a spectrum of inherited severe insulin resistance disorders. It is considered the mildest form, as symptoms often do not appear until puberty or later and are generally not life-threatening.
Symptoms
- Insulin resistance: The body’s tissues do not respond properly to insulin, impairing blood glucose regulation and leading to diabetes mellitus.
- Female-specific features: Many females experience primary amenorrhea (failure to begin menstruation by age 16) or light, irregular periods. They may also develop ovarian cysts and hirsutism (excessive body hair growth).
- Skin changes: Both males and females may develop acanthosis nigricans, where skin in body folds becomes thick, dark, and velvety.
- Weight: Unlike many other forms of insulin resistance, affected females are typically not overweight.
- Male-specific features: Symptoms in males are often more subtle, sometimes presenting only as low blood sugar (hypoglycemia) or diabetes mellitus in adulthood.
Causes
The syndrome is caused by mutations in the INSR gene, which provides instructions for making the insulin receptor. These receptors are found on the outer membrane of cells and are responsible for binding to insulin to trigger essential cell functions. Mutations result in a faulty receptor that cannot transmit signals properly, leading to severe insulin resistance despite the presence of insulin in the bloodstream.
Inheritance
Type A insulin resistance syndrome can be inherited in either an autosomal dominant or, less commonly, an autosomal recessive pattern. In dominant cases, one copy of the altered gene is sufficient to cause the disorder, while in recessive cases, both copies of the gene must be mutated.