Triple A syndrome (Allgrove syndrome) is a rare autosomal recessive disorder caused by mutations in the AAAS gene, characterized by the triad of achalasia, adrenal insufficiency, and alacrimia. It also associated with motor, sensory, and autonomic nervous system abnormalities. We performed longitudinal autonomic tests on a family affected by this syndrome.

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The proband is a 44-year-old woman with symptoms since age 8, including hypotension, achalasia, generalized weakness, and presyncope. Genetic testing confirmed AAAS-related Triple A syndrome, but there was no evidence of adrenal insufficiency. Her brother, the most affected, had severe achalasia, chronic respiratory insufficiency, hypotension, syncope, and pain, and he died at 35.

She underwent 5 autonomic tests over 30 years. Her brother underwent 2 autonomic tests over 6 years. All tests revealed consistent abnormalities: 1. Significant reduction in mean heart rate variation on deep breathing.; 2. Decreased Valsalva ratio.; 3. Significant orthostatic hypotension with compensatory tachycardia on the tilt test. Most of the patient’s QSART results were borderline normal, no significant reductions observed. However, her brother's tests showed almost absence of all QSART measurements.

Her less symptomatic sister underwent 3 autonomic tests, all of which revealed orthostatic hypotension with proper compensatory tachycardia during the tilt test. Additionally, the mean heart rate variation, Valsalva ratio, and QSART were within normal limits. The father had alacrimia, reduced sweat output on QSART, and pupillary hypersensitivity on pilocarpine test. He had normal mean heart rate variation, Valsalva ratio, and tilt test results.