Familial glucocorticoid deficiency
What is familial glucocorticoid deficiency?
Familial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body.
A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood sugar (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).
There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause.
How common is familial glucocorticoid deficiency?
The prevalence of familial glucocorticoid deficiency is unknown.
What genes are related to familial glucocorticoid deficiency?
Mutations in the MC2R, MRAP, and NNT genes account for the majority of cases of familial glucocorticoid deficiency; mutations in other genes, some known and some unidentified, can also cause this condition.
The MC2R gene provides instructions for making a protein called adrenocorticotropic hormone (ACTH) receptor, which is found primarily in the adrenal glands. The protein produced from theMRAP gene transports the ACTH receptor from the interior of the cell to the cell membrane. When the ACTH receptor is embedded within the cell membrane, it is turned on (activated) by the MRAP protein. Activated ACTH receptor can then attach (bind) to ACTH, and this binding triggers the adrenal glands to produce glucocorticoids. MC2R gene mutations lead to the production of a receptor that cannot be transported to the cell membrane or, if it does get to the cell membrane, cannot bind to ACTH. MRAP gene mutations impair the transport of the ACTH receptor to the cell membrane. Without the binding of the ACTH receptor to its hormone, there is no signal to trigger the adrenal glands to produce glucocorticoids.
The NNT gene provides instructions for making an enzyme called nicotinamide nucleotide transhydrogenase. This enzyme is found embedded in the inner membrane of structures called mitochondria, which are the energy-producing centers of cells. This enzyme helps produce a substance called NADPH, which is involved in removing potentially toxic molecules called reactive oxygen species that can damage DNA, proteins, and cell membranes. NNT gene mutations impair the enzyme's ability to produce NADPH, leading to an increase in reactive oxygen species in adrenal gland tissues. Over time, these toxic molecules can impair the function of adrenal gland cells and lead to their death (apoptosis), diminishing the production of glucocorticoids.
See a list of genes associated with familial glucocorticoid deficiency.
How do people inherit familial glucocorticoid deficiency?
This condition is inherited in an autosomal recessive pattern, which means 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 familial glucocorticoid deficiency?
These resources address the diagnosis or management of familial glucocorticoid deficiency and may include treatment providers.
- Genetic Testing Registry: ACTH
- Genetic Testing Registry: Glucocorticoid deficiency
- Genetic Testing Registry: Glucocorticoid deficiency
- Genetic Testing Registry: Natural killer cell deficiency, familial
You might also find information on the diagnosis or management of familial glucocorticoid deficiency 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 familial glucocorticoid deficiency?
You may find the following resources about familial glucocorticoid deficiency helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for familial glucocorticoid deficiency?
- ACTH resistance
- adrenal unresponsiveness to ACTH
- glucocorticoid deficiency
- hereditary unresponsiveness to adrenocorticotropic hormone
- isolated glucocorticoid deficiency
What if I still have specific questions about familial glucocorticoid deficiency?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
- What does it mean if a disorder seems to run in my family?
- What are the different ways in which a genetic condition can be inherited?
- If a genetic disorder runs in my family, what are the chances that my children will have the condition?
- Why are some genetic conditions more common in particular ethnic groups?
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding familial glucocorticoid deficiency?
adrenal glands ; apoptosis ; autosomal ; autosomal recessive ; cell ; cell membrane ; deficiency ;DNA ; enzyme ; failure to thrive ; familial ; gene ; glucocorticoid ; glucocorticoids ; hereditary ;hormone ; hypoglycemia ; immune system ; inherited ; kidney ; mitochondria ; nerve cell ;neurological ; nucleotide ; oxygen ; prevalence ; protein ; reactive oxygen species ; receptor ;recessive ; toxic
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (10 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