Neurological features in adult Triple-A (Allgrove) syndrome

J Neurol. 2012 Jan;259(1):39-46. doi: 10.1007/s00415-011-6115-9. Epub 2011 Jun 9.

Abstract

Triple-A or Allgrove syndrome is a rare multisystem disease classically associated with esophageal achalasia, adrenal insufficiency and alacrima. Here, we describe the poorly understood neurological characteristics often associated with this condition, through the clinical and electrophysiological analysis of eight patients. All patients were genetically confirmed and had a mutation in the ALADIN gene. They all displayed a classical picture of Triple-A syndrome: all suffered from achalasia and alacrima and half of them from adrenal insufficiency. However, all harbored a neurological picture characterized by a recognizable pattern of peripheral neuropathy. Other neurological features included cognitive deficits, pyramidal syndrome, cerebellar dysfunction, dysautonomia, neuro-ophthalmological signs and bulbar and facial symptoms. This neurological picture was prominent in all patients and misled the initial diagnosis in six of them, which had a late onset. We then review the previous neurological reports of this disease, to improve the understanding of this rare condition. Diagnosis of late-onset Triple-A syndrome is difficult when the clinical picture is mainly neurological and when endocrine or gastrointestinal signs are minor. The characteristics of the peripheral neuropathy, among other neurological signs, can be of help.

MeSH terms

  • Adrenal Insufficiency / diagnosis
  • Adrenal Insufficiency / etiology
  • Adrenal Insufficiency / genetics
  • Adrenal Insufficiency / pathology*
  • Adult
  • Age of Onset
  • Aged
  • Brachial Plexus Neuritis / etiology
  • Electrodiagnosis
  • Esophageal Achalasia / diagnosis
  • Esophageal Achalasia / etiology
  • Esophageal Achalasia / genetics
  • Esophageal Achalasia / pathology*
  • Female
  • Gait Disorders, Neurologic / etiology
  • Humans
  • Male
  • Middle Aged
  • Motor Neurons / physiology
  • Nervous System Diseases / pathology*
  • Peripheral Nervous System Diseases / etiology
  • Retrospective Studies
  • Thorax / abnormalities
  • Tongue / pathology
  • Young Adult

Supplementary concepts

  • Achalasia Addisonianism Alacrimia syndrome