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About SickKids

July 6, 2015

Surprising new cause of intestinal disease identified

SickKids study finds a defect in the blood vessels, not the intestine, may be to blame

Typically, when doctors come across a very young patient with severe diarrhea and bowel disease, they usually attribute the condition to a problem in the child’s gut. New research led by The Hospital for Sick Children (SickKids) reveals a surprising case report, in which the genetic defect responsible for the child’s illness actually resides in the blood vessels rather than the intestine, or gut. 

“Instead of an intestinal disease, we unexpectedly identified a vascular disease. This is an entirely new way of looking at intestinal disease including the protein loss from the bowel often seen in inflammatory bowel disease (IBD) and offers a promising new research focus,” says Dr. Aleixo Muise, Principal Investigator of the study, Clinician-Scientist and Co-Director of the SickKids IBD Centre.

The study is published in the July 1 online edition of Cellular and Molecular Gastroenterology and Hepatology.

The patient described in this case study presented with severe diarrhea, weight loss and poor feeding. A number of vital proteins commonly found within the blood were undetectable in this patient. Because the disease was seen at a very early age and was quite severe with uncharacteristic features, the team used Next-Generation Sequencing to look at the part of the genome which codes for proteins, the exome.

Remarkably, a mutation within a gene called Plasmalemma Vessicle Associated Protein, or PLVAP was detected. This protein acts like a filter which covers the holes in certain types of blood vessels, keeping important proteins in the blood. Dr. Abdul Elkadri, first author on the study, and Clinical Fellow in Gastroenterology, Hepatology and Nutrition at SickKids, explained that the novel mutation resulted in the absence of PLVAP protein leading to the loss of the protein filter in the bowel, explaining why this child had undetectable amounts of other crucial blood proteins.

“Sadly, this patient died, but what the team has learned thanks to this case will help to identify, diagnose and care for similar cases much more quickly,” says Muise.

He explains that this finding introduces a new mechanism and category of diarrhea. Further research into this disease may lead to new treatments and a better understanding of other forms of diseases where there is severe protein loss.

The cartoon shows the mechanism that results in disease in our patient with PLVAP deficiency. The left depicts the normal openings (diaphragms) found in the intestinal vessels. The PLVAP protein forms the filter that prevents proteins from leaking into the gut. In the patient’s vessels (right), the filter is missing and proteins leak directly into the gut resulting in severe disease.
The cartoon shows the mechanism that results in disease in our patient with PLVAP deficiency. The left depicts the normal openings (diaphragms) found in the intestinal vessels. The PLVAP protein forms the filter that prevents proteins from leaking into the gut. In the patient’s vessels (right), the filter is missing and proteins leak directly into the gut resulting in severe disease.