Clinical response to the long acting somatostatin analogue SMS 201-995 in a child with congenital microvillus atrophy.

Abstract

SUMMARY A 27 month old girl with congenital microvillus atrophy received two courses of SMS 201-995, a synthetic long acting analogue of native somatostatin, in an attempt to decrease profuse secretory diarrhoea. During the first trial at 13 months of age fluid and electrolytes administered by parenteral infusion were decreased as measured by water and faecal electrolyte losses. During the second trial of SMS 201-995 at 19 months fluid and electrolyte input were held constant for 14 days. Stool volume declined from 275 ml/kg to 161 ml/kg. Reductions in output of stool electrolytes (Nal, K+, Cl-) were accompanied by an increase in urine fluid output and increased excretion of urinary Nal. Subsequent administration of SMS 201-995 for a nine month period was not associated with adverse side effects or an impairment of growth velocity. These findings suggest that SMS 201-995 may be useful therapy in infants with high output diarrhoea as a result of congenital microvillus atrophy.Congenital microvillus atrophy is a distinct clinical entity which presents with intractable watery diarrhoea in the first few days of life.' Histology of small intestinal mucosa shows severe villus atrophy without crypt hyperplasia or an inflammatory infiltrate in the lamina propria.' 2 Transmission electron microscopy of small intestinal and rectal mucosa is diagnostic because microvilli on the apical plasma membrane are either very shortened and irregular, or completely absent. In addition, microvillus inclusions consisting of intracytoplasmic vacuoles lined with microvilli are contained within the cytosol of enterocytes.' 2 The longterm prognosis in affected infants is extemely poor as they are completely dependent on parenteral alimentation for nutritional support and maintenance of hydration. All attempts at oral feeding increase the volume of stool output.2 Each of the patients first reported, died during their first year of life.' ' Despite attempts to modulate the diarrhoeal

Pathophysiology in Microvillus Inclusion Disease

“…All forms of pharmacological intervention to control watery diarrhea have failed including steroids, somatostatin analogues (octreotide), loperamide, or the administration of epidermal growth factor [3,22]. There are case reports where the stool output could be reduced by pharmacotherapy, but enteral nutrition was still not possible [23]. In single patients with mild symptoms, especially patients with a late onset or atypical form, spontaneous remission has been described [24].…”

Effect of Octreotide on Colonic Motility in Pediatric Patients With Chronic Recalcitrant Constipation

“…7 It has several gastrointestinal actions. [8][9][10][11] Octreotide induces phase III of the migrating motor complex in the small intestine. 12 Von der Ohe et al conducted a randomized blind study assessing the regional effects of octreotide on the gastrointestinal tract; the study showed improvement in the colonic motility index and statistically significant phasic pressure activity in the octreotide group compared to placebo.…”

Intractable Diarrhea in a Newborn Infant: Microvillous Inclusion Disease

“…Empirical trials of various medical therapies, including high dose corticosteroid, pentagastrin, human colostrum, epidermal growth factor, clonidine, and somatostatin or its long acting analogue octreotide, have been reported (1)(2)(3)(4). Of these, only somatostatin or its analogue octreotide was effective in decreasing the volume of diarrhea and preventing recurrent episodes of dehydration (24). However, in no instance has medical therapy prevented reliance on parenteral nutrition and intravenous fluid replacement therapy for massive, ongoing intestinal losses.…”