A genetic form of achlorhydria and gastritis: Reply to Schiffmann.
John S. Fordtran, M.D.
Betesh, A. L., C. A. Santa Ana, J. A. Cole and J. S. Fordtran (2015). “A genetic form of achlorhydria and gastritis Reply.” American Journal of Clinical Nutrition 102(6): 1615-1616.
We thank Schiffmann for calling attention to congenital achlorhydria in patients with mucolipidosis type IV (MLIV). As he and his coworkers at the NIH clearly showed, these patients secreted no gastric acid after maximal stimulation with pentagastrin. Although gastric biopsy samples revealed a normal density of parietal cells, they were distended with vacuoles. In addition, mucosal atrophy in the gastric fundus was mild in a 4-y-old patient, moderate in a 7-y-old patient, and severe in a 22-y-old patient. Antral biopsies revealed no gastritis. Half of the patients had iron deficiency anemia, and 24-h urinary iron excretion was low in all of the patients. None of the patients had occult blood in their stools. The anemia responded to oral iron therapy. Achlorhydria is the presumed primary event in this association between iron deficiency anemia and achlorhydria, and the above findings are consistent with the hypothesis that achlorhydria can cause malabsorption of dietary iron that results in iron deficiency anemia. It is possible that fundic mucosal atrophy in these patients with MLIV may predispose them to pernicious anemia in later life. The results of Schiffmann et al. also indicate that this lysosomal disease is a cause of chronic gastritis and achlorhydria. Therefore, we wish to modify point number 6 in the final paragraph of our article to include MLIV as a third known cause of chronic gastritis in patients with achlorhydria. A mechanistic distinction should be made between the chronic gastritis and achlorhydria that occurs in patients with autoimmunity and Helicobacter pylori compared with that in patients with MLIV. In the former 2 conditions, gastritis is the cause of achlorhydria. In contrast, in MLIV, achlorhydria is apparently primary and is the presumed cause of fundic gastritis. It seems likely that additional clinically important insights would be gained if the mechanism can be determined by which MLIVinduced achlorhydria causes fundic gastritis. Although we know of no convincing evidence that chronic suppression of gastric acid secretion by proton pump inhibitors or by H2 receptor antagonists leads to fundic gastritis and atrophy in humans, inhibition of acid secretion by such drugs is probably less severe and less consistent than it is in patients with MLIV. Studies in guinea pigs have shown ultrastructural changes in parietal cells following administration of omperazole. There was no evidence of such damage when similar experiments were conducted in rabbits.