What is Allgrove Syndrome (3A syndrome (AAA))?
Allgrove syndrome, also known as 3A syndrome (AAA), was first identified in 1978. This condition is identified by three main components: resistance to the hormone known as adrenocorticotrophic hormone (ACTH) which can lead to adrenal insufficiency, a condition where the adrenal glands do not produce enough hormones; alacrimia, or a lack of tears; and achalasia, a problem with the throat that makes swallowing difficult. Some patients with Allgrove syndrome may also have progressive neurological issues, which could include mental retardation to a certain degree.
The syndrome seems to be inherited in an autosomal recessive manner. This means that both parents must carry the faulty gene and pass it on to their child. In cases where parents are blood relatives (consanguinity) or there are siblings who have been affected before, the risk of developing the syndrome increases.
The signs and symptoms of Allgrove syndrome usually depend on the age of the patient. Eye abnormalities can be present at birth. However, adrenal and gastrointestinal issues (related to the digestive system) typically become noticeable after six months up to the first ten years of life. Neurological dysfunction, stemming from issues in the central or autonomic nervous system, is also common in Allgrove syndrome and is often noticed during adolescence.
What Causes Allgrove Syndrome (3A syndrome (AAA))?
Allgrove’s syndrome is caused by changes in a gene known as AAAS. This gene, located on chromosome 12q13, creates a protein called ALADIN and is highly active in various human tissues.
There is evidence that the region of 12q13 on the chromosome is directly linked with Allgrove syndrome. The disease can gradually result in the loss of functions controlled by certain nerve cells.
People with Allgrove syndrome, who have these genetic changes often have issues with how their body works, even though there might not be any visible changes to their body’s structure.
Risk Factors and Frequency for Allgrove Syndrome (3A syndrome (AAA))
Allgrove syndrome is a medical condition that is inherited from both parents (autosomal recessive inheritance) and has a varied set of symptoms. It’s very hard to say how often it occurs because symptoms can vary a lot from person to person. If both parents are carriers, there’s a 25% chance their child will have the condition. People of Black, Native American, Arabic, and Asian descent are often reported with this syndrome, affecting both males and females. The onset of symptoms varies – adrenal insufficiency (a condition where the adrenal glands don’t produce enough hormones) often doesn’t show up until the first two decades of life. In contrast, alacrima (a condition affecting tear production) usually shows up in early infancy, and achalasia (a difficulty in swallowing) can occur as early as 6 months or as late as late adolescence.
Signs and Symptoms of Allgrove Syndrome (3A syndrome (AAA))
When a person seeks medical assistance for conditions like Triple A syndrome, a few symptoms are commonly observed. These may include:
- Dry eyes at birth because they don’t produce tears (alacrima)
- Difficulty feeding
- Frequent vomiting
- Weight loss due to swallowing issues (achalasia)
- Seizures as a result of low blood sugar from adrenal issues
- Delayed growth and development
Additional signs that could help doctors recognize this condition earlier are:
- Family history of consanguinity (marriage or reproduction between close blood relatives)
- Symptoms of autonomic failure like low blood pressure when standing (orthostatic hypotension)
- Developmental delays or intellectual disabilities
- Seizures
- Similar medical issues in siblings
- Distinguishing physical features including a smaller head, thin face with a pronounced groove above the upper lip, postural changes, nasal-sounding speech, unsteady movement, skin thickening that causes cracks in the hands and feet
Additionally, a specific eye examination may show abnormal results in the Schirmer’s test, which measures tear production, and the presence of damage to the cornea, the front surface of the eye.
Testing for Allgrove Syndrome (3A syndrome (AAA))
Doctors utilize laboratory tests to detect any potential problems, even though these test results don’t specifically point to a certain condition. A Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP) can help reveal if the patient is suffering from protein-calorie malnutrition. These tests look at a variety of things, including red and white blood cells, glucose (sugar) levels, and kidney function.
In patients with Allgrove syndrome, it’s crucial to examine the levels of ACTH, cortisol, and the results of an ACTH stimulation test to identify adrenal insufficiency, which is an issue with the adrenal glands not making enough hormones. In addition, testing the aldosterone and renin levels can help identify mineralocorticoid deficiency, a hormonal imbalance that affects salt and water balance in the body.
Other tests like lumbar puncture and baseline blood glucose can also help provide clues about the cause of seizures, which are sudden, uncontrollable electrical disturbances in the brain. Esophageal motility tests, which assess how the muscles and nerves in the esophagus work, are recommended for patients showing signs of achalasia, a disorder that affects the ability of the esophagus to move food into the stomach.
There are additional diagnostic tools that doctors use depending on the symptoms. For example, if a patient is having seizures or other neurological symptoms, doctors prefer options like a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain. These are both imaging tests that help doctors examine the structures within the brain.
If a patient is suspected of having achalasia, a barium esophagogram is often performed. This is an X-ray of the esophagus taken after the patient swallows a barium solution. Other options include esophageal manometry and endoscopy, which are procedures to assess the functionality of the esophagus.
For those having trouble with tear production (alacrima), doctors will examine the eye using tests such as the Schirmer test, slit-lamp examination, and fluorescein staining. This helps them assess tear production and eye health in general.
Finally, for patients expressing hearing deficits, Brainstem Auditory Evoked Response (BAER) testing may be practical. BAER testing is a method to evaluate the nerve pathways of hearing.
Treatment Options for Allgrove Syndrome (3A syndrome (AAA))
Hydrocortisone is usually the first choice of medication when treating children for Allgrove syndrome, also known as Triple A Syndrome. This is because it has an ideal balance of effects on mineralocorticoids and glucocorticoids. These are two types of hormones that help regulate the body’s metabolism, inflammation, immune response, and many aspects of salt and water balance in the body. However, sometimes another medication called fludrocortisone is required to supplement the activities of mineralocorticoids in the body. Other alternatives to hydrocortisone could be prednisone and dexamethasone, especially in patients who might have difficulty following prescribed medication routines. However, close monitoring of weight and physical development is necessary for patients taking prednisone and dexamethasone, because these medications can suppress growth and last longer in the body.
Patient with a symptom called alacrima, a condition where they produce fewer tears than normal, are generally recommended to use eye lubricants regularly for protection against cornea damages caused by constant dry eyes.
If surgery is needed for patients with Allgrove syndrome, they should be given additional doses of glucocorticoids to cope with the physical stress from surgery.
In cases where a patient is facing difficulty swallowing due to achalasia, a condition where the esophagus is unable to move food normally into stomach, a procedure known as pneumatic dilatation is often used to relieve the muscle spasms causing the issue. However, if this dilatation procedure is unsuccessful, an alternative operation called an anterior cardiomyotomy, or a Heller procedure, might be necessary. This operation, though effective, carries risks such as esophageal rupture and increased possibility of complications after the surgery.
For those with severe dry eye (alacrima) not responding to topical eye lubricants, a procedure to block tear drainage (punctal occlusion) can improve their symptoms.
What else can Allgrove Syndrome (3A syndrome (AAA)) be?
These are some medical conditions that involve the adrenal gland:
- Adrenal hypoplasia
- Familial glucocorticoid deficiency
- Addison disease
What to expect with Allgrove Syndrome (3A syndrome (AAA))
The outlook of a condition heavily relies on identifying it early and managing it effectively. The top reason for fatalities is an unnoticed adrenal crisis, where the adrenal glands don’t produce enough hormones. This often presents as a hypoglycemic seizure, which is a seizure triggered by low blood sugar, early in the disease progression.
Possible Complications When Diagnosed with Allgrove Syndrome (3A syndrome (AAA))
Complications are largely due to the traditional signs and symptoms of AAA syndrome or from the treatment. Overuse of a type of medication called glucocorticoids can lead to growth problems and a condition known as Cushing syndrome. On the other hand, not using enough steroids can cause a medical crisis involving low blood pressure, low blood sugar, and an increased risk of death.
Another symptom, Alacrima, can cause a condition known as dry eye syndrome. Achalasia, another symptom, can lead to recurrent aspiration, choking, and lung inflammation. Other possible complications include issues with the automatic nervous system, lack of coordination, developmental delay, and mental retardation.
Common Complications:
- Overuse of glucocorticoids leading to growth failure and Cushing syndrome
- Undertreatment with steroids resulting in adrenal crisis (low blood pressure, low blood sugar, higher risk of death)
- Alacrima leading to dry eye syndrome
- Achalasia causing recurrent aspiration, choking, and lung inflammation
- Other complications like autonomic neuropathy, lack of coordination, developmental delay, and mental retardation
Preventing Allgrove Syndrome (3A syndrome (AAA))
Allgrove syndrome is a condition that can often lead to adrenal insufficiency, a condition where your adrenal glands don’t produce enough hormones, causing weakness and intense fatigue. This is usually the main reason why patients with Allgrove syndrome experience health problems, and why it can sometimes be life-threatening. To manage this, it’s crucial to take medication known as glucocorticoids correctly and regularly, as advised by the doctor.
Patients should wear medical bracelets or necklaces that say “adrenal insufficiency” all the time, so that in case of a health emergency, the responders would be aware of their condition. Doctors and medical personnel should educate parents about the importance of having injectable steroids at home in case of emergencies or when medical personnel aren’t available.
It’s also critical to prevent potential eye problems by consistently using eye lubricants. These lubricants keep the eyes moist and help prevent infections and corneal ulcers, which are sores on the front part of the eye that can be caused by dryness. Regular check-ups with an eye specialist is needed to monitor this.
Patients and their families should be aware of the risk factors for gastroesophageal reflux disease, which is a digestive disorder that occurs when acidic stomach juices, or food and fluids back up from the stomach into the esophagus. This is particularly important for those with a condition called achalasia, where the esophagus is unable to move food into the stomach properly. If the patient has symptoms like recurrent vomiting, cough, or difficulties in eating, they should see their doctor right away.
