Wernicke’s encephalopathy in a patient with triple A (Allgrove) syndrome

Abstract

Triple A syndrome (AAAS, Allgrove syndrome, OMIM 231550) is a rare autosomal recessive disease characterized by the classic triad of alacrima, achalasia and adrenocorticotrophic hormone (ACTH)-resistant adrenal insufficiency. Recently, the underlying gene was identified on chromosome 12q13 [6, 12] and the gene product was named ALADIN (alacrima, achalasia, adrenal insufficiency, neurologic disorder) [3, 10]. The protein is highly expressed in neuroendocrine cells, intestinal tissue, and brain. It is assumed that involvement of the nervous system is a primary feature of the underlying genetic defect, but regarding neurological and autonomic dysfunctions, patients show a highly variable phenotype. There is only a small correlation between phenotype and genotype, even in siblings [4, 5, 8]. Therefore, additional unfavorable effects on appearance and progress of the symptoms must be assumed. Wernicke’s encephalopathy (WE) is an often unrecognized, potentially fatal disease with a triad of mental status changes, ocular abnormalities, and gait ataxia. Although WE is often associated with chronic alcohol abuse, it may occur in everyone who develops thiamine deficiency [2]. To our knowledge, the appearance of WE in a patient with AAAS has not been previously reported. We describe a case with a gastrointestinal dysfunction beyond reported feature of achalasia in AAAS and discuss a possible role of thiamine deficiency regarding the progress of neurologic disorders in patients with AAAS. A 34 year-old female patient with known AAAS was admitted with fatigue syndrome and dizziness that had been worsening for 5 days. For the 2 weeks previous to admission, the patient had refused to eat due to her father’s death. Additionally, she had not increased her daily corticosteroid medication of 15/5/5 mg hydrocortisone although it was a very stressful episode. After having been admitted, the patient suffered from diplopia. Neurological examination revealed upbeat nystagmus, horizontal gaze palsy, worsening of gait ataxia, and mild confusion. Actual neurophysiologic examinations confirmed previously known predominant axonal motor neuropathy with mild sensory abnormalities, delayed central motor function, and a markedly impaired parasympathetic and sympathetic autonomic function. Exacerbation of chronic adrenal insufficiency caused by pneumonia was initially suspected. The patient received 2 g ceftriaxone per day and 100 mg hydrocortisone intravenous in descending dosage to prevent Addison’s crisis. MRI of the brain was conducted for assignment of ocular abnormalities, ataxia and confusion. T2-weighted FLAIR images revealed signal elevation in the medial thalami and periaqueductal gray, which is compatible with H. Kunte (&) A. Numann L. Harms Department of Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany e-mail: hagen.kunte@charite.de