Triple A or Allgrove syndrome (AS) (MIM 231550) is a rare autosomal recessive disorder of adreno cortico tropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrimia (1). While alacrimia is often present at birth, and if untreated may lead to acute keratopathy and corneal ulcerations (2), achalasia manifests with age with dysphagia and feeding difficulties together with adrenal insufficiency (3, 4). This core phenotype may evolve with progressive neurological degeneration, cutaneous alterations (palmoplantar hyperkeratosis), short stature and osteoporosis (5–7), the first cause of death being an undiagnosed ‘adrenal crisis’. AS is caused by mutations in the AAAS gene (8–10), encoding Aladin, a member of the nucleoporin family at the nuclear pore complex (NPC), composed of a central 170-aa domain with four WD repeats (11). Nucleoporins play a crucial role in transport processes between nucleus and cytoplasm, while Aladin interaction with the NPC suggests a role as a structural scaffold (12, 13). No clear genotype–phenotype correlations have been established in AS (14), and lack of AAAS gene mutations in some AS patients suggested genetic heterogeneity (5, 15).
Two Italian patients with novel AAAS gene mutation expand allelic and phenotypic spectrum of triple A (Allgrove) syndrome
CALABRESE, Olga;FERLINI, Alessandra;
2010
Abstract
Triple A or Allgrove syndrome (AS) (MIM 231550) is a rare autosomal recessive disorder of adreno cortico tropic hormone (ACTH) resistant adrenal insufficiency, achalasia and alacrimia (1). While alacrimia is often present at birth, and if untreated may lead to acute keratopathy and corneal ulcerations (2), achalasia manifests with age with dysphagia and feeding difficulties together with adrenal insufficiency (3, 4). This core phenotype may evolve with progressive neurological degeneration, cutaneous alterations (palmoplantar hyperkeratosis), short stature and osteoporosis (5–7), the first cause of death being an undiagnosed ‘adrenal crisis’. AS is caused by mutations in the AAAS gene (8–10), encoding Aladin, a member of the nucleoporin family at the nuclear pore complex (NPC), composed of a central 170-aa domain with four WD repeats (11). Nucleoporins play a crucial role in transport processes between nucleus and cytoplasm, while Aladin interaction with the NPC suggests a role as a structural scaffold (12, 13). No clear genotype–phenotype correlations have been established in AS (14), and lack of AAAS gene mutations in some AS patients suggested genetic heterogeneity (5, 15).I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
