Allgrove (AAA) Syndrome Clinical Presentation

Updated: Mar 15, 2021
  • Author: Robert J Ferry, Jr, MD; Chief Editor: Robert P Hoffman, MD  more...
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Presentation

History

At presentation, review of systems may be positive for alacrima, hyperpigmentation, developmental delay, seizures, dysphagia, hypernasal speech, and symptoms related to orthostatic hypotension.

Many cases of Allgrove (AAA) syndrome present with classic symptoms of primary adrenal insufficiency and alacrima, [16] including hypoglycemic seizures and shock. Esophageal achalasia in pediatrics is rare, with less than 5% of patients presenting under the age of 15 years. [13] Achalasia typically presents with vomiting (84.6%), dysphagia (69.2%), weight loss (46.0%), and chronic cough (46.1%). [17] Often misdiagnosed as gastroesophageal reflux, achalasia should be considered as a differential in GERD unresponsive to treatment. [13]

A family history of early unexplained infant deaths and familial consanguinity provides important clues. Evaluate siblings for early signs, particularly alacrima because this defect is considered to be an early symptom of Allgrove syndrome, and may appear during early infancy.

Although mental retardation and hyperpigmentation in the parents or grandparents of patients have been reported, these are not common or consistent findings and are not expected with autosomal recessive inheritance.

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Physical Examination

A distinct facial appearance associated with Allgrove syndrome consists of a long thin face with a long philtrum, narrow upper lip, and a down-turned mouth. These features are not seen in unaffected siblings. [18]

Microcephaly is associated frequently with this disorder, but whether this is a primary manifestation or simply a reflection of recurrent hypoglycemia and/or malnutrition is unclear.

Conjunctival injection and irritation may be the only obvious signs of alacrima. Slit lamp examination may reveal punctate keratopathy or corneal ulceration. [19]

Definitive diagnosis of alacrima can be made at bedside with the Schirmer test. This test evaluates the wetting of a special strip placed in the conjunctival sac for 5 minutes. Less than 10 mm of wetting is abnormal.

Cardiac examination findings may be abnormal due to a number of autonomic nervous system defects that may accompany Allgrove syndrome. Orthostatic hypotension and diminished heart rate variations during deep breathing and Valsalva maneuver are well documented. Abnormal findings on respiratory examination may be secondary to recurrent aspiration accompanying achalasia.

Skin examination of patients may reveal abnormal findings that assist in confirming diagnosis. Hyperpigmentation is common but may be observed less frequently than in other forms of primary adrenal failure. Hyperkeratosis and fine fissuring of the palms of the hands and soles of the feet represent a unique feature of this syndrome.

Adults may exhibit progressive neural degeneration, develop parkinsonian features, and show mental deterioration. Neurologic features are varied and have been the subject of several case reports and reviews. [20] A complete neurologic evaluation and developmental study may highlight the impaired neurologic and developmental function associated with this syndrome. Palatopharyngeal incompetence, sensory impairment, ataxia, and muscle weakness are among the documented findings. [21]

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