pseudo-Hirschsprung's Disease Research Articles

RET promoter variations in familial African degenerative leiomyopathy (ADL): first report of a possible genetic-environmental interaction

African degenerative leiomyopathy (ADL, DL, Bantu pseudo-Hirschsprung's disease) is a distinctive visceral myopathy, of unknown etiology, occurring in Africa. It has a classical clinical and histologic picture in young indigenous African children. It presents as intestinal pseudo-obstruction with a massive megacolon due to degeneration of smooth muscle without aganglionosis. Because of its late presentation and geographical and ethnic distribution, it is thought to be an acquired degenerative hollow visceral myopathy. Only one previous report of familial recurrence exists. The main Hirschsprung susceptibility gene RET is a potential candidate gene in this condition, because of its role in the development of the intrinsic innervation and ganglia of the smooth muscle layers of the gastro-intestinal tract. We report a second case of familial ADL recurrence and explore possible etiologic causes including variations of the RET gene. Multiple variations in the RET promoter were identified in this case which leads to the possibility of a genetic-environmental predisposition for this condition. We therefore hypothesize that RET may play a modulating role in ADL susceptibility (and possibly other visceral myopathies). It is possible that subtle malformations in the ENS may result from RET dysfunction which then predisposes the individual to environmental influences which initiate the later onset of muscle degeneration.

Megacolon in an Adult Case of Hypoganglionosis, a Pseudo-Hirschsprung's Disease: An Autopsy Study

We report an autopsied 20-year-old man case of intestinal necrosis associated with megacolon from hypoganglionosis, a pseudo-Hirschsprung's disease. The patient had suffered from severe constipation since two years of age, and presented abdominal distention from age ten. Autopsy revealed marked dilatation and necrosis of the entire large intestine. Although ganglion cells in the intestinal plexus were found throughout the large intestine, their number was reduced to 12-20% of that in the normal control. In pseudo-Hirschsprung's disease, there are occasional cases where an acute abdomen first presents itself in adulthood after running its course as chronic constipation.

Two-dimensional demonstration of myenteric nerve plexus: Aplication for pseudo-Hirschsprung's disease

The use of two-dimensional demonstration of myenteric nerve plexus for the morphological estimation of pseudo-Hirschsprung's disease is introduced. By fluorescent immunohistochemistry for S-100 protein on flat-mounted frozen sections, a decrease in the amount of ganglionic plexuses in the small intestinal segments in cases of pseudo-Hirschsprung's disease was able to be distinguished from normoganglionic plexuses in control cases. Moreover, a morphological difference between the two types of cases was clearly demonstrated. This method may be an indispensable tool in the reliable diagnosis of pseudo-Hirschsprung's disease.

Clinical, laboratory and prognostic features of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease).

One hundred and forty-eight cases of congenital large intestinal motor dysfunction (pseudo-Hirschsprung's disease) were reported by members of the Japanese Society of Pediatric Surgeons during the past 20 years. The disorder was defined as a congenital, non-mechanical obstruction of the intestine with the presence of intramural ganglia in the terminal rectum. Intramural ganglia were abnormal in 77 cases, normal in 42, and could not be determined in 29. Of those with abnormal intramural ganglia, 54 had immature ganglia or hypoganglionosis (oligoganglionosis), 15 had neuronal intestinal dysplasia, and eight had a segmental anomaly. Of those with a normal myenteric plexus, 22 had chronic and twelve had suspected idiopathic intestinal pseudo-obstruction syndrome; eight had megacystis-microcolon-intestinal hypoperistalsis syndrome. While cases with both hypoganglionosis and normal intramural ganglia had normal acetylcholine esterase activity, a significantly greater number of patients with hypoganglionosis lacked normal rectoanal reflexes. Patients with hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction syndrome, and megalocystis-microcolon-intestinal hypoperistalsis syndrome had poor prognoses with an overall mortality of 36.9%. These findings indicate that congenital large intestinal motor dysfunction remains a serious disease of childhood.

Histological Investigation of the Myenteric Plexus of the Entire Gut in an Infant with Hypogenesis of the Intestine

A male infant with pseudo-Hirschsprung's disease was treated for 2 years and 10 months, then died of severe enterocolitis. At autopsy examination of the entire gut was possible, and a definite histological examination could be performed which threw light on the pathogenesis. The ganglion cells of the esophagus, stomach, small intestine, colon and rectum were examined, diameters of their nuclei were measured, and their nuclear volumes were calculated. S-100 and anti-neurofilament stainings were also performed in an immunohistological investigation of the glial cells and nerve fibers. Both the diameter of the volume of the nuclei of the ganglion cells in the small intestine and colon were significantly smaller than normal. Even in the esophagus the nuclear volume was smaller than normal. The glial cells and nerve fibers gradually decreased in the caudal direction. Thus, histomorphometry and immunohistochemistry both showed that the neuroblasts in the intestine were immature and the migration of ganglion cells was disturbed in this case. The final diagnosis was hypogenesis of the intestine.

Pseudo-Hirschsprung's disease: S. Goto, K. Ikeda, T. Kaneko, et al. J Jap Soc Pediatr Surg 17:1285–1290, (December), 1981

Pseudo-Hirschsprung's disease: S. Goto, K. Ikeda, T. Kaneko, et al. J Jap Soc Pediatr Surg 17:1285–1290, (December), 1981

Histologic studies of rectocolic aganglionosis and allied diseases

It is well-known that some patients exhibiting the symptoms of Hirschsprung's disease are shown to have intramural ganglia in the distal myenteric plexus. Some of them have been described as "pseudo-Hirschsprung's disease". It is likely that a variety of conditions have been included in this group. Using a silver impregnation technique we have made a detailed histologic study of the rectum and large bowel in a number of cases with provisional clinical diagnosis of Hirschsprung's disease but in which rectal biopsy showed small ganglia in Meissner's plexus demonstrated by acetylcholinesterase (Ach-E) staining. Three histologic variations were shown that may be called hypoganglionosis, immaturity of ganglia, and hypogenesis. An attempt is made to relate their clinical picture to the histologic findings.

Seminar on pseudo-Hirschsprung's disease and related disorders : Arch. Dis. Child. 41:143, April, 1966

Seminar on pseudo-Hirschsprung's disease and related disorders : Arch. Dis. Child. 41:143, April, 1966

Some newer aspects on Hirschsprung's disease and allied disorders

Evidence in favor of the conception of a vascular disturbance as the cause of aganglionosis is presented. The pathophysiology of Hirschsprung's disease as evidenced from studies on the effects of aganglionosis on the contents of substance P and cholinesterase in the bowel wall is reviewed and is correlated with histochemical studies on the sympathetic and the parasympathetic components of the intramural plexuses. A systematic survey of disease entities, resembling but not identical with Hirschsprung's disease is presented. The term pseudo-Hirschsprung's disease is suggested to cover this group of diseases.

Seminar on pseudo-Hirschsprung's disease and related disorders.

Seminar on pseudo-Hirschsprung's disease and related disorders.