Primary Immunodeficiency with Pneumocystis Susceptibility, Type 2 (PIPS2)
Primary Immunodeficiency with Pneumocystis Susceptibility is a genetic disorder that greatly increase the risk for Pneumocystis pneumonia and other types of infections. This primary (aka hereditary) immunodeficiency disorder causes a combined immunodeficiency, meaning that the function of both T and B lymphocyte, two types of white blood cell that are important to fighting off infections, are affected.
Who gets PIPS2?
PIPS2 was first discovered in a Cavalier King Charles Spaniel. It is caused by a mutation in the CARMIL2 gene. The inheritance of the disorder is autosomal recessive. This means that only dogs with two copies of the mutation are affected.
At this time, we have not identified the PIPS2 mutation in other breeds. Therefore, if you are interested in testing a dog that is not a Cavalier King Charles Spaniel, we encourage you to contact us first at [email protected] to obtain information on the likelihood that the mutation exists in your breed of interest.
What are the clinical signs of PIPS?
PIPS predisposes to recurrent bacterial, fungal, and viral infections. Respiratory infections (e.g., pneumonia) are common with both PIPS1 and PIPS2. Pneumocystis pneumonia is a strong indicator of an underlying immunodeficiency, as this fungal infection does not occur in animals with a healthy immune system. PIPS1 also predisposes to infectious diarrhea from parasites or bacteria. With PIPS1 and PIPS2, diarrhea can also occur from development of autoimmune disease, such as inflammatory bowel disease. Skin allergies and skin infections are common with PIPS2 but less common with PIPS1.
How is PIPS managed?
There is no cure for PIPS. However, once diagnosed, there are management strategies that might help. For example, affected dogs should avoid environments where there is high risk for infectious disease transmission, such as kennels, dog shows, and dog parks. Veterinary care should be sought immediately if respiratory signs (e.g., cough, difficulty breathing), skin abnormalities (e.g., new wound, red area), or diarrhea develops. Standard vaccination recommendations can be followed, but vaccine response might not be fully normal in affected dogs.
Xanthinuria (XU2b)
Hereditary xanthinuria is an autosomal recessive genetic disorder that results in excessive xanthine (a metabolic byproduct) in the urine. This increases the risk for formation of xanthine bladder or kidney stones and can cause significant kidney disease. Hereditary xanthinuria is a result of mutations in either xanthine dehydrogenase (XDH, type 1 xanthinuria) or molybdenum cofactor sulfurase (MOCOS, type 2 xanthinuria). Xanthinuria can also occur from non-genetic factors such as exposure to drugs that inhibit XDH (e.g. allopurinol). This is termed iatrogenic xanthinuria.
Who gets it?
Hereditary xanthinuria is rare but has been reported in multiple breeds. In the past 5 years, the Minnesota Urolith Center received xanthine stone submissions from dogs of the following breeds with suspected hereditary xanthinuria: Toy Manchester Terrier, Cavalier King Charles Spaniel, English Cocker Spaniel, Dachshund, Chihuahua, and mixed breed dogs.
To date, we have identified causative mutations in a mixed breed dog (Type 1a), Toy Manchester Terriers (Type 2a), English Cocker Spaniels and Cavalier King Charles Spaniels (Type 2b), and Dachshunds (Type 2c). If you are submitting a sample from a breed that is not listed, we recommend running all four tests. Genetic test results can be used to help guide medical management of affected dogs, identify dogs at risk even before they form stones, and to inform breeding decisions.
What are the clinical signs?
Xanthinuria leads to the development of urinary stones. This causes irritation that may manifest as straining to urinate, frequent urination, urgency with urination, blood in the urine, or life-threatening urinary obstructions. Microscopic crystals can also accumulate in the kidney and cause kidney disease. Patients with xanthinuria can present at virtually any age from a few months onwards. Though many patients have serious consequences, some remain asymptomatic. Males appear to be more likely to form stones than females.
How is it managed?
Once diagnosed, stones can be treated surgically or with other removal techniques, but the disease tends to recur without additional intervention. High fluid intake is important, along with a low purine diet. Therapeutic veterinary low purine diets are available by prescription. Egg, nuts, and dairy are generally low purine sources of protein; foods with high purine content such as liver, kidney, bacon, and most seafood should be avoided.
Submitting a sample
Step 1 - Select instructions for your sample type
- Blood sample protocol (pdf)
- Cheek swab protocol (pdf)
- Dew claw & tail docking protocol (pdf)
- Semen sample protocol (pdf)
Step 2 - Complete your submission form(s)
Step 3 - Fees & Payment
Any single test
- 1-3 Dogs - $65 each
- 4 or more - $58 each
Any 2 tests "combo"
- 1-3 Dogs - $100 each
- 4 or more - $85 each
Need cheek swabs?
Cheek swabs are not included in the purchase price. Links to several purchasing options are available within the cheek swab protocol (pdf).
Step 4 - Ship your sample(s)
Result interpretation
Scientific references
- A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia. Coffey, E.L.; Ma, L.; Cissé, O.H.; Kovacs, J.A.; Minor, K.M.; Sukura, A.; Danesi, P.; Friedenberg, S.G.; Cullen, J.N.; Weissenbacher-Lang, C.; et al. J. Fungi 2024, 10, 198. https://doi.org/10.3390/jof10030198
- Multiple variants in XDH and MOCOS underlie xanthine urolithiasis in dogs. Nicole M. Tate, Katie M. Minor, Jody P. Lulich, James R. Mickelson, Allyson Berent, Jonathan D. Foster, Kasey H. Petersen, Eva Furrow. Molecular Genetics and Metabolism Reports, Vol 29, 2021, 100792. doi: 10.1016/j.ymgmr.2021.100792
- Three diverse mutations underlying canine xanthine urolithiasis. E. Furrow, N. Tate, K. Minor, J. Mickelson, K. Peterson, and J. Lulich. ACVIM Research Report, 2016.