Motor neuropathy and alacrima: oligosymptomatic triple A syndrome

Abstract

Triple A (Allgrove) syndrome (MIM #231550) is characterized by achalasia, alacrima, adrenal insufficiency, and a progressive neurological syndrome manifesting mostly within the first decade and comprising cerebellar ataxia, peripheral neuropathy and mild cognitive impairment. Recently, mutations of the AAAS gene on chromosome 12q13 have been discovered to cause this autosomal recessively inherited condition. We report a 14-year-old girl who from her preschool age suffered from slowly increasing muscle weakness in arms and legs and wasting predominantly of the gastrocnemii muscles. Nerve conduction studies revealed a motor axonal neuropathy. In addition, an impaired tear production had been noted already in her first months of age that was classified as sicca syndrome. However, there was complete absence of tears and thus alacrima. This uncommon association prompted mutation analysis of the AAAS gene that revealed a compound heterozygous mutation. In exon 2, a heterozygous G>A transition was found leading t o a premature stop codon (W84X) that had been described in other triple A patients before. On the other allele a previously unreported T>C transition was detected in exon 14 which results in an amino acid change (L430F). Just recently the girl complained of swallowing difficulties, and contrast oesophagram as well as oesophageal manometry revealed mild achalasia. Adrenal function is normal at present, but adrenal insufficiency will probably manifest during the next years. Our observation demonstrates that oligosymptomatic variants of triple A syndrome occur with motor axonal neuropathy and alacrima as sole symptoms. It is important to enquire about tear production and swallowing difficulties in children with axonal neuropathy and to perform mutation analysis of the AAAS gene in clinically suspected triple A syndrome.