The document summarizes a study that investigated the histopathology of the cardia (esophagus) in 10 children with Allgrove's syndrome (also known as triple A syndrome). The key findings were: 1) Fibrosis of the intermuscular plane was prevalent in all patients. 2) Myenteric ganglia were absent, decreased, or apparently normal in most patients. 3) Neuronal nitric oxide synthase was absent or decreased in most patients. 4) Lymphocytes infiltrating the myenteric plexus were present in many patients.

1. Achalasia of the Cardia in Allgrove's (Triple A) Syndrome: Histopathologic Study of 10 Cases<br />Khelif, Karim M.D.; De Laet, Marc-Henri M.D.; Chaouachi, Beji M.D.; Segers, Valérie M.D.; Vanderwinden, Jean-Marie M.D., Ph.D.<br />Abstract<br />Allgrove's syndrome, i.e., achalasia, addisonianism, alacrima (OMIM 231550) is an autosomal recessive disorder recently associated with the AAAS gene coding for the Aladin protein. However, the pathophysiology of achalasia in Allgrove's syndrome remains obscure. Here we investigated the histopathology of the cardia in Allgrove's syndrome. Myectomy specimens from 10 children with Allgrove's syndrome and four normal cardia were studied by routine staining and by immunohistochemistry for the pan-neuronal marker PGP9.5, neuronal NO synthase, interstitial cells of Cajal, and CD3+ lymphocytes. In the normal cardia, myenteric ganglia, intramuscular nerve fibers, and interstitial cells of Cajal were numerous, whereas myenteric fibrosis and lymphocyte infiltrates were absent. In Allgrove's syndrome, fibrosis of the intermuscular plane was prevalent in all patients. Myenteric ganglia were absent, decreased, or apparently normal in 1 of 10, 8 of 10, and 1 of 10, respectively. Neuronal NO synthase was absent in 7 of 10 and decreased in 3 of 10, whereas interstitial cells of Cajal appeared normal in 7 of 10 and decreased in 3 of 10. Lymphocytes infiltrating the myenteric plexus were present in 6 of 10. Pyloromyectomy specimens available for six patients showed normal histopathologic features. In conclusion, the lack of neuronal NO synthase and fibrosis of the intermuscular plane can be linked to the defective cardia relaxation. Other features were less constant and may reflect the variability of disease expression and progression among patients with Allgrove's syndrome.<br />Achalasia of the cardia is a rare disorder in children. It is characterized by a defective relaxation of the cardia and absence of peristalsis in the esophageal body. Achalasia sometimes occur as part of a variable, autosomal recessive, disorder termed Allgrove's syndrome (AS) or triple A syndrome (3A) 2 (OMIM 231550), which features achalasia, addisonianism (ACTH insensitivity), and alacrima (lack of tears). Furthermore, late-onset progressive neurologic symptoms have been reported, suggesting that the central nervous system may also be involved in AS. 13,14,32 AS has been linked to chromosome 12q13. 15,30,35 Recently, a triple A syndrome (AAAS) gene has been identified on chromosome 12q13. Mutations of the AAAS gene leading to the presumptive lack of function of the encoded protein (known as Aladin or Adracalin) are thought to be responsible for AS. 16,32 However, the pathophysiology of AS remains obscure, and very little is known about the histopathologic features of the cardia in AS. Here we have investigated the histopathology of the cardia in AS.<br />