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Triple A syndrome

Other Names for this Disease
  • 2A syndrome
  • 3A syndrome
  • 4A syndrome
  • AAA
  • AAA syndrome
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What are the signs and symptoms of Triple A syndrome?

Triple A syndrome is characterized by three specific features: achalasia, Addison disease, and alacrima (reduced or absent ability to secrete tears). Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is alacrima. Most people with triple A syndrome have all three of these features, although some have only two.

Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia). People with this condition may have other neurological abnormalities such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time. People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition.

Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. Individuals typically develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.[1] Cases of parkinsonism, peripheral neuropathy, and seizures developing in individuals have been reported, but whether this also occurs in individuals who received an early diagnosis and long-term effective medical and surgical management is unclear.[2]
Last updated: 2/9/2011

The Human Phenotype Ontology provides the following list of signs and symptoms for Triple A syndrome. If the information is available, the table below includes how often the symptom is seen in people with this condition. You can use the MedlinePlus Medical Dictionary to look up the definitions for these medical terms.

Signs and Symptoms Approximate number of patients (when available)
Generalized hyperpigmentation 90%
Primary adrenal insufficiency 90%
Seizures 90%
Palmoplantar keratoderma 50%
Short stature 50%
Visual impairment 50%
Anterior hypopituitarism 7.5%
Developmental regression 7.5%
Hyperreflexia 7.5%
Incoordination 7.5%
Iris coloboma 7.5%
Muscular hypotonia 7.5%
Optic atrophy 7.5%
Respiratory insufficiency 7.5%
Abnormality of vision evoked potentials -
Achalasia -
Adrenocorticotropin (ACTH) receptor (ACTHR) defect -
Anisocoria -
Ataxia -
Autosomal recessive inheritance -
Babinski sign -
Childhood onset -
Dysarthria -
Dysautonomia -
Hyperpigmentation of the skin -
Hyperreflexia -
Hypocortisolemia -
Intellectual disability -
Motor axonal neuropathy -
Muscle weakness -
Optic atrophy -
Orthostatic hypotension -
Palmoplantar hyperkeratosis -
Progressive disorder -
Short stature -

Last updated: 3/1/2015

The Human Phenotype Ontology (HPO) has collected information on how often a sign or symptom occurs in a condition. Much of this information comes from Orphanet, a European rare disease database. The frequency of a sign or symptom is usually listed as a rough estimate of the percentage of patients who have that feature.

The frequency may also be listed as a fraction. The first number of the fraction is how many people had the symptom, and the second number is the total number of people who were examined in one study. For example, a frequency of 25/25 means that in a study of 25 people all patients were found to have that symptom. Because these frequencies are based on a specific study, the fractions may be different if another group of patients are examined.

Sometimes, no information on frequency is available. In these cases, the sign or symptom may be rare or common.

  1. Triple A syndrome. Genetics Home Reference. February 2010; Accessed 2/7/2011.
  2. Bruce A Boston, Daniel L Marks. Allgrove (AAA) Syndrome. eMedicine. February 20, 2009; Accessed 2/7/2011.

Other Names for this Disease
  • 2A syndrome
  • 3A syndrome
  • 4A syndrome
  • AAA
  • AAA syndrome
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.