Genomic coordinate (human 12:53,307,455 AAAS).
Cytoband (human 12q13.13 AAAS).
Here I present: “Allgrove (AAA) Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966.
INTRODUCTION.
Allgrove syndrome, is an inherited autosomal recessive disorder caused by mutations in the AAAS gene. It gets its name from three cardinal features: Achromasia (adrenal insufficiency), Achalasia, and Alacrima.
Core Manifestations:
Most individuals display all three of the following features, though severity and age of onset vary widely:
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Alacrima (Lack of tears): Often the earliest symptom, manifesting in infancy or early childhood. It results in dry eyes and requires consistent artificial tear drops to prevent corneal damage.
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Achalasia: A disorder of the esophagus that prevents it from properly moving food into the stomach. It causes severe difficulty swallowing, vomiting, and weight loss, typically managed with interventions like balloon dilation.
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Achromasia (Adrenal Insufficiency): A lack of hormone production by the adrenal glands (specifically ACTH-resistant adrenal failure). This can lead to fatigue, low blood pressure, and life-threatening adrenal crises that require immediate steroid replacement therapy.
Neurological & Associated Symptoms:
Because the condition causes a progressive neurological syndrome, some experts refer to it as “4A syndrome”. Common associated features include:
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Autonomic dysfunction: Problems with unconscious bodily functions (e.g., sweating abnormalities, pupil dilation issues).
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Peripheral polyneuropathy: Numbness, weakness, and motor or sensory deficits in the limbs.
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Other signs: Some patients experience cognitive deficits, optic atrophy, short stature, or osteoporosis.
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