Axonal neuropathy with unusual pattern of amyotrophy and alacrima associated with a novel AAAS mutation p.Leu430Phe.

[triple a syndrome]

The triple A syndrome is caused by autosomal recessively inherited mutations in the AAAS gene and is characterized by achalasia , alacrima and adrenal insufficiency as well as progressive neurological impairment . We report on a 14 -year -old girl with slowly progressive axonal motor neuropathy with conspicuous muscle wasting of hypothenars and calves as well as alacrima . The mutation analysis of the AAAS gene revealed a compound heterozygous mutation : a c .251 G >A mutation in exon 2 that had been reported previously , and a novel c .1288 C >T mutation in exon 14 . At the transcriptional level , the c .251 G >A transition results in an aberrant splicing and decay of this RNA strand so that the particular clinical picture results from the novel c .1288 C >T , (p .Leu 430 P he , L 430 F ) mutation in a hemizygous form . With transfection experiments , we demonstrate that GFP-ALADIN (L 430 F ) correctly localizes to nuclear pore complexes . Therefore , we conclude that this point mutation impairs ALADIN function at the nuclear pore .