Triple-A Syndrome

The Triple-A (Allgrove) syndrome is characterized by the triad of familial adrenoinsufficiency due to corticotropin (ACTH) resistance, achalasia (swallowing difficulties), and alacrima (deficient secretion of tears). The disorder usually manifests within the first decade of life with alacrima and/or achalasia, followed by glucocorticoid deficiency. Life-threatening complications include hypoglycemic episodes and severe feeding difficulties. Affected individuals typically have several additional clinical concerns, such as progressive peripheral and/or autonomic neuropathy, punctate palmoplantar keratoderma (patches of callused skin on palms and soles), dry mouth, angular cheilitis and fissured tongue, mild mental retardation, osteoporosis and, rarely, short stature. The pattern and severity of neurologic and autonomic dysfunction in Triple-A syndrome is quite variable, including hyperreflexia, impaired visual evoked potentials, optic nerve atrophy, anisocoria (unequal pupil size), abnormal sweating, postural (orthostatic) hypotension with compensatory tachycardia, muscle weakness, ataxia, parkinsonism, and motor peripheral neuropathy. Hence the clinical diagnosis of Triple-A syndrome may be difficult. Because autonomic neuropathy and amyotrophy (muscle wasting) appear to be integral features of this disorder, the name “4A syndrome” has been considered.

Tests Available

Forms and Documents

Test Details

AAAS
  • Confirmation of a clinical diagnosis
  • Carrier testing in unaffected family members
  • Recurrence risk calculation
  • Prenatal diagnosis in families with an affected child and known mutation(s)
  • Capillary Sequencing

Ordering

219
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81479x1
No
Yes
  • 255.4 Corticoadrenal insufficiency
  • 530 Diseases of esophagus Excludes: esophageal varices (456.0-456.2)
  • 337 Disorders of the autonomic nervous system Includes: disorders of peripheral autonomic, sympathetic, parasympathetic, or vegetative system Excludes: familial dysautonomia [Riley-Day syndrome] (742.8)
  • 356 Hereditary and idiopathic peripheral neuropathy
* For price inquiries please email zebras@genedx.com

References

  1. Houlden H et al. (2002) Brain 125: 2681-90
  2. Qin K et al., (2007) Mol Genet Metab 92(4):359-63
  3. Milenkovic T et al., (2010)Eur J Pediatr. 169(11):1323-8
  4. Sandrini F et al., (2001) J Clin Endocrinol. 86: 5433-7
  5. Brooks BP et al., (2005) Clin Genet. 68: 215-21