Skip to Main Content

At a glance

This inherited disorder is most likely a variant of ☞Allgrove Syndrome (Achalasia-Alacrima-Adrenocorticotropic hormone [ACTH] Insensitivity Syndrome; Triple A-Syndrome). However, in a small minority it can be an acquired abnormality induced by the formation of antibodies that block ACTH receptors. In contrast to Addison Syndrome, the renin-angiotensin-aldosterone axis functions normally.

Synonym

Double-A Syndrome.

Genetic inheritance

Autosomal recessive. Similar to ☞Allgrove Syndrome, the responsible mutations affect the AAAS gene encoding Aladin (adracalin) on chromosome 12q13. Aladin is a nuclear envelope protein and part of the nuclear pore complex. Parental consanguinity is considered to be a risk factor.

Diagnosis

Based on the clinical findings of absent tears, dysphagia, and failure to thrive.

Clinical aspects

The disorder is characterized by absent tears and achalasia and is usually progressive, with symptoms that are often not yet present in the first few months of life. Mental retardation and progressive central, peripheral, and autonomic nervous system dysfunctions are common later on. A predominantly axonal motor neuropathy affecting upper and lower limbs is typical with distal muscle weakness and wasting as well as mild sensory abnormalities. Other autonomic nervous system anomalies may include orthostatic hypotension, disturbances of heart rate and diminished response to external vasopressors, an abnormal sweating response and sexual impotence. Megaesophagus secondary to a lack of ganglion cells and nerve fibers in the lower esophagus (achalasia) may occur. Other associated features may include microcephaly, short stature, osteoporosis, palmoplantar and punctate hyperkeratosis, hyperpigmentation of the skin, angular cheilitis, xerostomia, glossitis, and fissured or atrophic tongue. Ophthalmic manifestations other than alacrimia may include atrophy of the lacrimal glands, keratoconjunctivitis sicca, accommodation and pupillary abnormalities, (eg, sluggish or tonic pupils, hypersensitivity to miotics), optic nerve atrophy, and photophobia.

Precautions before anesthesia

In the presence of Addisonian Syndrome, either check ☞Addisonian Syndrome or ☞Allgrove Syndrome for additional information with regards to precautions before anesthesia and anesthetic management. Check serum electrolytes and blood glucose levels. Obtain a history of vomiting, reflux, dysphagia, and potential aspiration pneumonia. Check for signs of autonomic dysfunction.

Anesthetic considerations

Fluids (saliva) and food can pool or get trapped above the lower esophageal sphincter in achalasia patients, hence a rapid sequence induction is strongly recommended. The likelihood of corneal abrasions is increased due to alacrimia. The potential for autonomic dysfunction and cardiovascular instability with a decreased response to vasopressors exists. Pupillary response to light might be abnormal, which should be documented preoperatively and kept in mind when assessing neurologic function intra- or postoperatively. Insertion of a transesophageal echocardiography probe (or even nasogastric tube) may not be feasible and should be tried very carefully and gently (with ample lubricant) in patients with achalasia.

Pharmacological implications

Because of reduced muscle ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.