Long Term Follow-Up of Clinical and Electromyoneurographical Abnormalities in Eight Croatian Patients with Triple A Syndrome (P01.126)

Abstract

Objective: To analyse long term follow up of neurological abnormalities (during 2 years to 23 years) in eight Croatian patients with triple A syndrome. Background The triple A syndrome is caused by autosomal recessively inherited mutation in AAAS gene on chromosome 12q13 encoding the nuclear pore protein ALADIN. This multisystem disease is characterized by achalasia, alacrimia, adrenal insufficiency and neurological impairment. Design/Methods: Clinical examination, electromyoneurography (EMNG) and molecular genetic analysis were performed in eight patients with triple A syndrome (five males and three females). Results: At the time of diagnosis all patients (aged 2 years to 8 years) presented with alacrimia, latent or manifest adrenal insufficiency, anisocoria in 2, optic atrophy in 4, motor and sensory polyneuropathy on the first exam in 2 siblings, muscle weakness and hypotrophy of distal muscle groups, cavus feet, hyperreflexia but absent triceps surae jerks, talocrural joints contractures, tremor and dysmetria in 5 patients. First EMG findings were normal at the age 6-11 years in 6/8 patients. The follow up EMG showed chronic partial denervation in all patients. Spontaneous activity (fibrillations) was registered in 3/8, compound muscle action potentials (CMAP) were polyphasic in 6/8 patients. Absent or low CMAP amplitude (0-0,5mV) was obtained in 6/8, decreased motor conduction velocity (29-40 m/s) in 8/8, absent F-wave potentials in 7/8, absent neural potentials in 5/8, and proximal conduction block in 5 patients. Mutation pSer263Pro was identified in 5 of 8 patients. One is homozygous and four are compound heterozygous for this mutation. Genotype/phenotype analysis confirmed lack of correlation in patients with triple A syndrome. Conclusions: Long term follow up neurography in patients with triple A syndrome showed progressive mixed motor and sensory polyneuropathy development with signs of pronounced demyelination and/or probably secondary axonal damage. Molecular results support the hypothesis that the pSer263Pro mutation is founder mutation in Slavic population. Disclosure: Dr. Barisic has nothing to disclose. Dr. Dumic has nothing to disclose. Dr. Kusec has nothing to disclose. Dr. Stingl has nothing to disclose. Dr. Lehman has nothing to disclose. Dr. Bunoza has nothing to disclose. Dr. Grdan has nothing to disclose. Dr. Koehler has nothing to disclose. Dr. Heubner has nothing to disclose.