Menekse Öztürk (Düsseldorf / DE), Dr. med. Christopher Nelke (Düsseldorf / DE), PD Dr.rer nat Andreas Roos (Essen / DE), Univ.-Prof. Dr. med. Dr. rer. nat. Sven G. Meuth (Düsseldorf / DE), PD Dr. med. Tobias Ruck (Düsseldorf / DE)
Abstract-Text (inkl. Referenzen)
Introduction
Triple-A syndrome (AAAS) is a rare autosomal recessive congenital disorder. The clinical hallmark of AAAS is the concurrent manifestation of achalasia, alacrimia and adrenal insufficiency. Additional neurological manifestations may include autonomic dysfunction, peripheral neuropathy, amyotrophy or bulbar symptoms. AAAS is exceedingly rare with only around 100 cases reported. The AAAS gene encodes the protein ALADIN, a member of the WD-repeat (tryptophan- aspartic acid) family of regulatory proteins. Here, we report on a novel distinct case of AAAS in a female patient.
Method
Past medical history and clinical examination with review of the literature was gathered. Molecular gene analysis by DNA sequencing was performed.
Results
A 47-year-old female patient expressed signs of gait impairment, speech disorder and alacrimia from the age of two years. Neurological symptoms affecting both first and second motor neuron emerged. Distally accentuated paresis with fine motor impairment was observed. Amotile achalasia requiring pneumatic dilatation with dysphagia and reflux esophagitis was noticed. A homozygous AAAS variant c.307+4_307delAGTA was detected.
Summary
The detected AAAS variant has not been previously reported and thus extends the molecular genetic landscape of the disease. Given the distinct clinical phenotype, we suspect that this AAAS variant is pathogenic providing the molecular underpinnings for the observed clinical syndrome. Mechanistic experiments are ongoing.