Yorkshire Terrier Vol. 4, No. 1 I December 2011 Researchers Seek Candidate Genes for Protein-Losing Enteropathy esearchers at Cornell University developing lymphangiectasia than can be developed that would identify School of Veterinary Medicine in other breeds. affected dogs and thus provide a diag - RIthaca, N.Y., are working to find Recognizing the widespread nostic tool for the disease. Currently, candidate genes that predispose York - occurrence of PLE in the breed, the the only definitive test to detect and shire Terriers to protein-losing enteropa - Yorkshire Terrier Club of America and distinguish between different causes thy (PLE), a potentially fatal condition the Yorkshire Terrier Club of America of PLE is an intestinal biopsy that is in which dogs lose significant protein Foundation recently helped fund an expensive, requires general anesthesia into their gastrointestinal system. AKC Canine Health Foundation grant and carries some health risks. While genetics are likely to play a that supports the Cornell University The severity of PLE varies among role in determining which dogs are research. The researchers’ ongoing individual dogs and may be related predisposed to developing PLE, envi - efforts to collect DNA samples from to differences in genetic expression ronmental factors, such as enteric affected and normal dogs are instru - of the disease. Some dogs show no (intestinal) bacteria or food intolerance mental to the success of the study. clinical signs, yet die quickly. Others or allergy, may contribute as well. “Our goal is to identify a gene change exhibit serious manifestations, but The extent to which environmental or set of changes that predispose a with proper disease management do factors influence the disease is not dog to PLE,” says lead investigator well. Diarrhea, anorexia, vomiting, fully known. Nate Sutter, Ph.D., assistant professor lethargy, weight loss, edema (swelling) In Yorkshire Terriers, PLE is widely of medical genetics. “The evidence or ascites (fluid in the abdominal attributed to lymphangiectasia, a that PLE has a genetic component cavity), and respiratory difficulty condition in which the lymph vessels primarily rests on the observation that from fluid in the chest are not become dilated and disrupt the normal some breeds — such as Yorkies — are uncommon signs in dogs with PLE. flow of lymph throughout the body. at an elevated risk for the disease. The Other at-risk breeds for PLE are Recent studies have showed extensive simplest explanation is that at-risk Basenji, Chinese Shar-Pei, Norwegian cystic dilatation of the intestinal crypts breeds have one or more genetic Lundehund and Soft-Coated Wheaten (mucosal glands of the epithelial lining factors that confer risk.” Terrier. The genetic basis for the dis - of the small intestine) also may con - Ultimately, once a genetic marker ease may vary by breed. Besides lym - tribute to PLE. One study showed that is identified and the causative muta - phangiectasia, conditions that can Yorkies have a tenfold greater risk of tion for PLE is discovered, a DNA test Continued on page 2 Managing a Lifelong Condition the specialist recommended an intestinal biopsy to determine definitively whether Winnie had PLE. rotein-losing enteropathy associated with lymphan g- Only weeks after the first signs of PLE, Winnie died Piectasia and crypt cysts is a fatal condition in as many of peritonitis following the intestinal biopsy procedure. as half or more Yorkshire Terriers, experts estimate. Most “It was probably a result of the disease causing changes diagnosed dogs receive lifelong therapy. Some dogs never that weakened the intestinal walls,” Fallon says. improve despite therapy, while others continue to live a “Chloe,” a 12-year-old Yorkshire Terrier owned by Jane normal, active life. Here are stories of the journeys of Downey of Columbus, Ohio, continues to thrive despite owners whose Yorkshire Terriers were diagnosed with PLE. having been diagnosed with PLE when she was 9 years Liz Youngblood of Seattle was pleased when her 7 1/2- old. “I have to work hard to keep Chloe’s weight down year-old Yorkie, “Taffy,” responded well to medications given with a strict diet,” Downey says. “She loves to get into to help reduce the signs of PLE. “In the beginning, Taffy the other dogs’ food bowls, so it’s a constant struggle. was well enough to play and enjoy herself,” she says. If she overeats, she gets bloated.” Not long afterward, diarrhea and fluid on the abdomen Another long-lived Yorkshire Terrier diagnosed with returned. “Then, Taffy began struggling to breathe,” says PLE is “Martha,” a retired conformation champion belong - Youngblood. “We had the fluid drained off several times, ing to Stephanie Ruiz of Orange County, Calif. Martha but it always came back.” was diagnosed at age 9 and today is 15. “When we The fluid-draining procedure was painful and put Taffy were still working on a diagnosis, we tried several diets at risk for peritonitis, or inflammation of the membranes for Martha, but none seemed to help,” Ruiz says. lining the abdomen. After seven months, Youngblood Once Martha was definitively diagnosed with PLE, the made the difficult decision to have Taffy euthanized. veterinarian prescribed medications to help manage signs Pancreatitis was the initial diagnosis given Denise of the disease. “The key for us is consistently following Fallon’s Yorkie, “Winnie,” who had lost her appetite and the veterinarian’s instructions regarding diet and medi ca - frequently vomited. After two weeks on a bland diet, tions,” says Ruiz. “Martha’s protein level is normal, and she Winnie continued to weaken. Fallon, of Mechanicsburg, has lived longer than any Yorkie we have ever owned.” Pa., was referred to a veterinary teaching hospital, where Researchers Seek Candidate Genes first, she didn’t eat well, even with an autosomal recessive or dominant continued from page 1 the prednisone. We could see she was inheritance pattern. wasting away and was losing muscle “Many Yorkshire Terriers with PLE lead to PLE are inflammatory bowel mass. We could see the bones in her succumb to the disease despite disease, intestinal lymphoma and fungal shoulders and feel her spine. We were aggressive therapeutic intervention,” infections such as histoplasmosis. so afraid we would lose her.” Simpson says. “The reasons for a good Dogs with PLE lose protein from the After a couple of weeks, the veteri - response versus a poor response are body through the intestines. Normally narian increased Phoebe’s prednisone. not clear.” the intestines absorb dietary protein “It was like magic,” says Fritz-Rubert. In the future, once sufficient num - from food during the digestive process, “Within five days, Phoebe went from bers of samples are collected, the team but the reverse happens in dogs with weighing 7 pounds to 5 pounds, and plans a genomewide association scan - PLE. In these dogs, the protein is she lost 4 inches around her belly. The ning that will help them to identify released into the intestines and lost weight loss was because her ascites regions of genes that vary among in feces. improved.” affected and healthy Yorkies. “This Several months after Phoebe was genetic assay provides genotypes Signs of a Similar Condition diagnosed with PLE, good news came from roughly 170,000 SNP (single Chronic occasional vomiting was nucleotide polymorphism) markers,” common in Julie Fritz-Rubert’s 4 ½- Sutter explains. “These markers occur year-old Yorkshire Terrier, “Phoebe.” How to Contribute to PLE all over the dog genome and give us When the dog vomited six times in Genetic Research a nice survey picture of an individual one day, she became concerned. A dog’s genome. few days later, the dog’s abdomen reeders and owners of Yorkshire “Each SNP marker on the chip has appeared bloated. “I took Phoebe to BTerriers can contribute DNA two allele forms. If we find a SNP the veterinarian, who suspected she samples to help advance genetic marker allele, or form, in affected had gastroenteritis but ran blood research at Cornell University School dogs that is not present in healthy work to be sure,” says Fritz-Rubert of Veterinary Medicine to identify dogs, we could have a correlation of Sacramento, Calif. candidate genes that cause protein- between the genotype and the dis - The blood test showed that Phoebe losing enteropathy (PLE). The ease phenotype. Since we know the had low levels of albumin and globulin, researchers are requesting samples genomic location for each SNP, we consistent with PLE. The veterinarian from affected dogs of all ages and could then look at the location, or recommended an intestinal biopsy to from older, healthy dogs. locus, in the genome for clues about determine definitively whether Phoebe For information about the criteria the disease.” had lymphangiectasia or another cause to qualify and how to submit samples Next, the researchers will zero in of PLE. The biopsy confirmed that Phoebe and pedigree and clinical informa - on that locus to make a finer grained had mild to moderate lymphangiectasia. tion, please contact Dr. Kenneth map showing differences and to help The lymph vessels in Phoebe’s body Simpson at [email protected] or identify the location more precisely. were dilated due to pressure from 607-253-3567, or Dr. Nate Sutter “Only after that step is completed inflammation. The lymph vessels in at [email protected]. will we be in a position to create a the intestines, called lacteals, were DNA test to help breeders gauge the not able to absorb dietary fat because risk for disease,” Sutter says. of increased intralymphatic pressure on a veterinary visit. “It turned out As the research continues, the goal with subsequent malabsorption of Phoebe had gained too much weight,” is to collect 100 samples of DNA from fat and other nutrients such as fat Fritz-Rubert says.