Triple A Syndrome:Ophthalmic Features and a Novel Mutation in the AAAS Gene

Abstract

Abstract: : Purpose: To describe unique ophthalmic features and a novel mutation of the AAAS gene in a subject with Triple–A syndrome (Allgrove syndrome, MIM 231550.) Triple A syndrome is an autosomal recessive condition characterized by adrenal insufficiency, alacrima, achalasia, and autonomic instability. Methods: Complete ophthalmic examination and mutation testing in the AAAS gene. Results: This 12 year–old subject presented with reduced tear production and corneal dryness, pupillary hypersensitivity to dilute pilocarpine, accomodative esotropia and accomodative dysregulation. MRI of the head showed hypoplastic lacrimal glands. Sequencing of the AAAS gene showed compound heterozygosity for a new, out–of–frame 5–bp deletion in exon 15, c1368–1372delGCTCA, and a previously–reported nonsence mutation in exon 9, C938C>T, R286X. Conclusions: Triple A syndrome can present with accomodative dysregulation, as well as tearing and pupillary abnormalities. The 5bp deletion in exon 15 of the AAAS gene is a novel mutation, predicted to cause loss of function of the ALADIN protein.

Keywords: mutations • strabismus: etiology • lacrimal gland