High ACTH, low cortisol, normal renin and aldosterone prove ACTH insensitivity, which along with achalasia and alacrima makes him a case of Allgrove/
triple A syndrome. Molecular genetic study for triple AS gene could not be done as it is not available in Pakistan.
The triple A syndrome gene, designated AAAS, localized on chromosome 12q 13 encodes for a 546 amino acid protein called ALADIN (Alacrimia-Achlasia-Adrenal Insufficiency and Neurologic disorder).
Based on presentation of achalasia, alacrima and adrenal insufficiency, diagnosis of triple A syndrome was made.
Allgrove's syndrome is an autosomal recessive disorder with varied presentations.14,15 Recent studies have identified mutation in AAA syndrome of a candidate gene on chromosome 12 q 13 in these patients.16 Prpic et al (2003) demonstrated marked phenotypic variability in three patients with genetically confirmed triple A syndrome. Two patients had achalasia, alacrima and adrenocortical deficiency as well as neurologic and autonomic dysfunction, third patient had achalasia and neurologic dysfunction only.
Linkage of the gene for the triple A syndrome to chromosome 12q13 near the type II keratin gene cluster.
Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.
The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proc Natl Acad Sci.
The triple A syndrome is due to mutations in ALADIN, A novel member of the nuclear pore complex.