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GTR Home > Tests > AAAS Gene Sequencing

Indication

This is a clinical test intended for Help: Diagnosis, Mutation Confirmation, Pre-symptomatic, Risk Assessment, Screening

Clinical summary

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Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. 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 glucose (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 a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two.\n\nMany 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).\n\nPeople 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.\n\nPeople 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.\n\nAlacrima 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. They 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. [from MedlinePlus Genetics]

Clinical features

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Imported from Human Phenotype Ontology (HPO)

  • Adrenal insufficiency
  • Anisocoria
  • Cerebellar ataxia
  • Dysarthria
  • Abnormal autonomic nervous system physiology
  • Achalasia
  • Orthostatic hypotension
  • Palmoplantar keratosis
  • Optic atrophy
  • Babinski sign
  • Muscle weakness
  • Hyperreflexia
  • Hyperpigmentation of the skin
  • Alacrima
  • Short stature
  • Abnormality of visual evoked potentials
  • Global developmental delay
  • Decreased circulating aldosterone level
  • Decreased circulating cortisol level
  • Motor axonal neuropathy
  • Intellectual disability
  • Adrenocorticotropin receptor defect
  • Microcephaly
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Conditions tested

Target population

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Patients with symptoms suggestive of Achalasia-addisonianism-alacrimia syndrome.

Citations

Not provided

Clinical validity

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Not provided

Clinical utility

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Not provided

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