Type A insulin resistance syndrome

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Reviewed December 2014

What is type A insulin resistance syndrome?

Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high.

Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.

The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood sugar (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.

Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening.

Read more about Rabson-Mendenhall syndrome and Donohue syndrome.

How common is type A insulin resistance syndrome?

Type A insulin resistance syndrome is estimated to affect about 1 in 100,000 people worldwide. Because females have more health problems associated with the condition, it is diagnosed more often in females than in males.

What genes are related to type A insulin resistance syndrome?

Type A insulin resistance syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.

Most of the INSR gene mutations that cause type A insulin resistance syndrome lead to the production of a faulty insulin receptor that cannot transmit signals properly. Although insulin is present in the bloodstream, the defective receptors make it less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood sugar regulation and leads to diabetes mellitus. In females with type A insulin resistance syndrome, excess insulin in the bloodstream interacts with hormonal factors during adolescence to cause abnormalities of the menstrual cycle, ovarian cysts, and other features of the disorder.

This condition is designated as type A to distinguish it from type B insulin resistance syndrome. Although the two disorders have similar signs and symptoms, type B is not caused by INSR gene mutations; instead, it results from an abnormality of the immune system that blocks insulin receptor function.

How do people inherit type A insulin resistance syndrome?

Type A insulin resistance syndrome can have either an autosomal dominant or, less commonly, an autosomal recessive pattern of inheritance.

In autosomal dominant inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

In autosomal recessive inheritance, both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of type A insulin resistance syndrome?

These resources address the diagnosis or management of type A insulin resistance syndrome and may include treatment providers.

Genetic Testing Registry: Insulin-resistant diabetes mellitus AND acanthosis nigricans

You might also find information on the diagnosis or management of type A insulin resistance syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about type A insulin resistance syndrome?

You may find the following resources about type A insulin resistance syndrome helpful. These materials are written for the general public.

MedlinePlus - Health information (5 links)
Additional NIH Resources - National Institutes of Health (2 links)
Educational resources - Information pages (5 links)
Patient support - For patients and families (3 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for type A insulin resistance syndrome?

diabetes mellitus, insulin-resistant, with acanthosis nigricans
extreme insulin resistance with acanthosis nigricans, hirsutism and abnormal insulin receptors
insulin-resistance syndrome type A
insulin resistance syndrome, type A
insulin resistance - type A
insulin-resistant diabetes mellitus and acanthosis nigricans
type A insulin resistance

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about type A insulin resistance syndrome?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding type A insulin resistance syndrome?

acanthosis nigricans ; androgens ; autosomal ; autosomal dominant ; autosomal recessive ; cell ;cysts ; diabetes ; diabetes mellitus ; gene ; glucose ; gonadotropins ; hirsutism ; homeostasis ;hormone ; hyperglycemia ; hyperinsulinemia ; hypoglycemia ; immune system ; inheritance ;inherited ; insulin ; insulin resistance ; menstruation ; mutation ; ovarian ; pattern of inheritance ;protein ; puberty ; receptor ; recessive ; sign ; spectrum ; syndrome ; testosterone

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (3 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.