Infantile Hypertrophic Pyloric Stenosis and Achalasia: NO-Related or Non-Related Conditions?

Abstract

Background: The regulated ability of sphincters to relax allows adequate control of digestive transit. Relaxation of the lower esophageal sphincter (LES) is essential for esophageal emptying and, similarly, pyloric relaxation permits gastric emptying. When the relaxatory response of these sphincters is impaired, luminal transit is altered, as occurs in achalasia and hypertrophic pyloric stenosis. Nitric oxide (NO) has been identified as the main inhibitory neurotransmitter in both sphincteric regions. Moreover, the absence of NO synthase in the LES and the pylorus has been implicated in the pathogenesis of infantile hypertrophic pyloric stenosis (IHPS) and achalasia, respectively. Case Report: We present the case of a 12-year-old boy diagnosed with these two different conditions attributed to NO absence: IHPS and achalasia. Conclusion: To our knowledge this is the first time that such an association has been reported. Whether IHPS and achalasia have been associated in this patient by chance or because they share common pathophysiological mechanisms remains speculative, but is a tantalizing dilemma.

Late-onset primary gastric outlet obstruction—an unusual cause of growth retardation

“…Pyloric achalasia may be an appropriate terminology for this condition because there are few reports describing association of pyloric obstruction with and without muscular hypertrophy and esophageal achalasia in adolescents [3][4][5]. A thickened circular layer of muscularis propria forms the pyloric sphincter.…”

“…High-amplitude contractions in gastroduodenal junction uncoordinated with antral contractions are partially responsible for pylorospasm leading to IHPS [9][10][11]. Nitric oxide synthase deficiency leading to lack of locally available nitric oxide may cause failure of muscular relaxation and neuromuscular incoordination at pylorus [4,6,12]. Tack et al [13] have recently suggested that postinfectious dyspepsia, early satiety, weight loss, and vomiting are caused by dysfunction at the level of nitrergic neurons.…”

The pylorus

“…This is similar to achalasia and Hirschprung's disease 52,53 which are also characterized by functional obstruction from failure of relaxation. Intriguingly, IHPS and achalasia has been reported in the same patient 54 . These findings have to be tempered with the knowledge that networks of interstitial cells of Cajal continue to develop postnatally; 55 this in part may account for the good prognosis of patients with IPHS following appropriate treatment.…”

Achalasia: will genetic studies provide insights?

“…These include HSCR (MIM 142623) (including one report of two affected male siblings) (Kelly et al 1997;Kohler et al 2005), duplication of the pylorus (Gupta and Hollander 1977;Jorge and Diaz 1976), additional achalasia of the pylorus (Kalsbeek and Voortman 1980), hypertrophic pyloric stenosis (MIM 179000) (Castro et al 1997;Cataliotti et al 2002), esophageo-rectal syndrome (Shafik 2003), megacystis-microcolon-intestinal hypoperistalsis syndrome (MIM 249210) (Al Harbi et al 1999), and situs inversus viscerum (MIM 270100) (Spinelli et al 1991). …”