ABSTRACT
Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene, located on chromosome 12q13. We describe a 42-year-old patient who presented with neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction with significant central and peripheral nervous system involvement. She was later diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene identified two heterozygous mutations within exon 14 and its donor splice site (p.L430F-c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome should be suspected in patients with neurological impairment associated with two or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).
Subject(s)
Adrenal Insufficiency/genetics , Esophageal Achalasia/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Nerve Tissue Proteins/genetics , Nuclear Pore Complex Proteins/genetics , Adrenal Insufficiency/ethnology , Adrenal Insufficiency/metabolism , Adult , Autonomic Nervous System Diseases/genetics , Autonomic Nervous System Diseases/metabolism , Autonomic Nervous System Diseases/physiopathology , DNA Mutational Analysis , Esophageal Achalasia/ethnology , Esophageal Achalasia/metabolism , Exons/genetics , Female , Genotype , Heterozygote , Humans , Italy , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/physiopathology , RNA Splice Sites/genetics , SyndromeABSTRACT
We describe a 69-year-old woman with bilateral adrenal hemorrhage complicated with antiphospholipid syndrome (APS). She was hospitalized with nausea and vomiting in September 2003. Laboratory data demonstrated hyponatremia, hypoglycemia and prolongation of activated partial thromboplastin time (aPTT). Abdominal computed tomography showed bilateral adrenal enlargement. In October 2003, she demonstrated altered mental status with progressive hyponatremia, a high level of ACTH, and a low level of serum cortisol. She also showed thrombocytopenia, anti-cardiolipin IgG antibody, anti-beta2GPI antibody, and lupus anticoagulants. After four months, anti-cardiolipin IgG antibody was still positive. Based on these findings, she was diagnosed as having APS complicated with adrenal insufficiency due to hemorrhagic infarction. After treatment with corticosteroid, a low dose of aspirin and normal saline infusion, her condition quickly improved. Platelet counts and aPTT were also normalized. To our knowledge, this is the second Japanese case of APS complicated with bilateral adrenal hemorrhage. APS should be considered an important underlying cause of adrenal insufficiency.
