Allgrove syndrome with features of familial dysautonomia: a novel mutation in the AAAS gene.

[triple a syndrome]

Allgrove syndrome (or triple-A syndrome ) is a rare autosomal recessive disorder characterized by alacrima , achalasia , adrenal insufficiency (glucocorticoid in the majority of cases ) and autonomic /neurological abnormalities . This disease is now known to be caused by mutation in the AAAS gene located on chromosome 12 q 13 . Diagnosis should be readily available when the full-blown features are there , but it becomes less apparent when presentation is atypical or in the evolving process . We present a brother and sister (12 and 19 y old , respectively ) born to consanguineous parents of Palestinian origin with Allgrove syndrome . The index patient was erroneously diagnosed to be a case of familial dysautonomia before the diagnosis of adrenal insufficiency was made at the age of 7 .5 y , while his elder sister had only alacrima from birth and developed achalasia at the age of 15 y . She started to develop early evidence of adrenal disease at the age of 19 y . Both of them had neuroautonomic dysfunction . The diagnosis of Allgrove syndrome was confirmed in these two patients by studying the gene mutation in the family . The sequencing of the AAAS gene in the two patients identified a novel homozygous mutation within intron 5 (IVS 5 +1 G-->A ). Both parents as well as all three other children were heterozygous for the same mutation .These two cases illustrate the heterogenous nature and the intrafamilial phenotypic variability of Allgrove syndrome .