DNA test for Fanconi Syndrome

Tags

basenji, basenji health endowment, breeders, fanconi, health tests, orthopedic foundation for animals

Basenjis are vulnerable to a hereditary, incurable kidney disease called Fanconi Syndrome. However, there is a DNA test that is publicly available through the Orthopedic Foundation for Animals that can let you know if your dog is clear, a carrier, or affected by this simple recessive genetic disease. It is very easy to find out the Fanconi status of any dog, whether they are a breeding stud, dam, or a spayed or neutered pet.

We tested Bowpi back in March 2010 when only the linked marker test was available. Her results came back as probably clear. This was a great relief.

In August 2011, the specific DNA mutation for Fanconi was found and a direct test was made available, replacing the previous linked marker test. Since the Basenji Health Endowment was partially subsidizing dogs that had been previously tested, I submitted a request for a retest kit.

24 December 2011

For $65 USD (minus $15 for subsidized tests), you get a kit mailed directly to your home, containing:

• Your order form with pre-printed mailing labels
• Detailed instructions
• Test sample card in a little manila envelope
• Sterile applicator

29 December 2011

Dog not included. You provide your own.

The instructions are very clear. Just make sure that it’s been a couple hours since your dog has eaten. When ready, unwrap the sterile applicator…

Swab the inside of your dog’s mouth for several seconds to collect saliva and DNA.

Then press the moistened tip to the area indicated on the test card.

Reminds me of those Paint with Water kids’ activity books.

Then let the card air dry for about an hour, making sure that nothing else touches it while this happens.

When dry, the white areas will show where DNA was successfully transferred.

Then all you have to do is put the card in the little manila pocket provided, put that in another envelope (I re-wrapped the manila envelope in the weatherproof Tyvek sleeve that the OFA originally sent everything in), affix one of the pre-printed address labels and a stamp, and drop it in the mailbox!

You are e-mailed a personal link to track the status of your order. When results are processed (could take several weeks), they’ll automatically be posted at a unique public entry for each dog on the OFA website. For example, here is Bowpi’s direct link:

http://www.offa.org/display.html?appnum=1414418#animal

We have no AKC registration for her, no records of her sire or dam, and her birthdate isn’t even correct (I think I just selected one of the dates on her previous veterinary records, but even those didn’t match). You don’t need any of this information to request a test. However, Bowpi is still searchable in the database by her name and/or her breed alone.

She is spayed and just a pet, but I wanted to have the test done so that I could know what to anticipate in regards to her health. As you can see, it is a simple, inexpensive (relative to the peace of mind offered), non-invasive procedure.

This test is not provided by the vet. It is done at home. Any breeder that claims their dogs have been “vet-checked” for Fanconi is suspect. Any breeder who is in a position to say that they’ve never had a problem with Fanconi in their lines can surely afford the $65 per dog to demonstrate that this is true.

All Fanconi results are made available to the public. Owners do not have the option of keeping test results to themselves, even if they do not come out as desired. Therefore, if a breeder’s dogs are not in the database, and the breeder cannot or will not provide you the public link so you can verify testing for yourself, it is fair to assume that this Fanconi DNA test has not been done.

I can think of no good reason why any Basenji breeder would not be testing their breeding stock.

[EDIT 27 January 2012: We got Bowpi’s OFA certificate in the mail this week. She’s Fanconi clear!]

[EDIT 4 February 2012: OFA website currently states: “It has come to our attention that there are technical problems with the new Fanconi Syndrome test for Basenjis. The reasons for these problems are under investigation. We are temporarily suspending testing until these problems are solved.” Test kits cannot be ordered at this time.]

[EDIT from e-mail received 12 February 2012: “Fanconi testing has been resumed. The problem has been identified and a change in the sequencing process implemented. Fewer than 25 dogs, all originally read as affected, will require retesting.”]

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LINK/VIDEOS: Dr. Karen Becker interviews Dr. Jean Dodds

Tags

allergies, canine hypothyroidism, health tests, hemopet, rabies challenge fund, vet, veterinary endocrinology

from Youtube channel MercolaHealthyPets

LINKS: Breeder sites on hypothyroidism

Tags

basenji, breeders, canine hypothyroidism, health tests, orthopedic foundation for animals, rhodesian ridgebacks, shetland sheepdogs, thyroids

Photo taken 1 March 2011

I first heard about canine hypothyroidism from Basenji people. With a current rank of #29 on the the list of breeds at risk for thyroid disease according to statistics compiled by the Orthopedic Foundation for Animals, and #35 according to Michigan State University, Basenji breeders had reason to be concerned. No, they don’t top the list, nor is that an enviable position to be in (that honor goes to the English Setter). But if even one out of every 10 dogs was showing abnormalities in a condition that could be screened, seems like it’s worth the test to me.

So it looks like responsible breeders were and have long been testing thyroids. And breeder websites have been where I have found some of the most informative, publicly-accessible information on hypothyroidism and canine thyroid health. Here are some of the links that I have found to be helpful.

Apu’s Basenjis: Basenji Health
– Karen Christensen, who provided the article on Apu’s page, also wrote up an article for the New York-based Rip Van Wrinkle Basenji club magazine, The Wrinkler. A .pdf is available here.

sinbajé basenjis: Thyroid Problems of the Basenji Dog.
– As far as breeder sites go, this is one of the most well done that I’ve seen, hitting a perfect mix of personal and professional, providing a ton of great information without cluttered design.

Revodana Ridgebacks: Talking About Thyroid: Everything you didn’t know you needed to know
– via a breeder of Rhodesian Ridgebacks. The article is directed primarily at breeders, but also useful in differentiating all the different available tests.

Moonstruck Meadows: Canine Health Testing: OFA Thyroid Tests
– via a breeder of Shetland Sheepdogs, what to look for in proof that a breeder has done proper testing on a dog.

I’m sure there are more out there, but this is enough for now.

Thyrogloblin AutoAntibodies (TgAA)

Tags

allergies, canine hypothyroidism, hair loss, health tests, hemopet, hyperpigmentation, orthopedic foundation for animals, tgaa, thyroglobulin autoantibodies, thyroids

One of the tests that we ordered from Hemopet/Hemolife labs as part of their Thyroid 5 panel was TgAA, or thyroglobulin autoantibodies. Yeah, say that one three times fast.

Well, we ordered it, but I didn’t really understand what the measure was for, nor how to match it against the reference range; I just wanted to be thorough. To rehash, Bowdu’s test numbers from Hemopet looked like this:

• T4: 0.87 (reference range 0.80 ~ 3.80 μg/dL)
• Free T4: 0.53 (reference range 0.55 ~ 2.32 ng/dL)
• T3: < 10, verified by repeat analysis (reference range 30 ~ 70 ng/dL)
• Free T3: 1.9 (reference range 1.6 ~ 3.5 pg/mL)
• Thyroglobulin Antibodies: <1% (reference range: negative [?])

TGAA CONFIRMATORY TEST INTERPRETATION
less than 10% = NEGATIVE 10 ~ 25% EQUIVOCAL greater than 25% = POSITIVE

I didn’t understand why the reference range was supposed to be “negative,” since a number that’s less than 1% is still a “positive” number. At any rate, Bowdu’s TgAA results fell within the reference range, while the others were low enough to diagnose him with hypothyroidism. How did his TgAA relate to the diagnosis?

Well, I’ve done some reading and poking around, and so I’m going to take a stab at rendering my understanding of what TgAA is and what those test results meant. If any experts are reading this and found that I’ve misunderstood what I’ve researched, please let me know. This is NOT my field by a long shot!

Photo taken 4 February 2011

Thyrogloblin AutoAntibodies (TgAA) are present in the system when the dog’s thyroid basically starts attacking itself, when something starts to go wrong with the thyroid glands. If a dog tests positive for TgAA, and other values are low, a dog is said to have autoimmune thyroiditis — the body is basically obstructing its own normal thyroid function. If other values are low, and TgAA is negative, it is labeled idiopathic thyroiditis — there’s some other reason that the thyroid production has atrophied. OR it could be that the condition has already progressed for some time such that you’re actually looking at the end stage of autoimmune thyroiditis, which is what I think is happening with Bowdu given his age and history of symptoms.

Some people called TgAA the “best” test in pinpointing thyroid dysfunction. As I understand it, it’s certainly not enough on its own. TgAA is the best advance indicator of possible thyroid disease further down the road, because if a dog is going to develop thyroid problems, he may test positive for TgAA as early as 1 year old, even without exhibiting other clinical symptoms or low T4 or T3 levels (subclinical thyroiditis). If TgAA comes back positive, it is “highly suggestive of later development of clinical hypothyroidism” (Ferguson, 658), though visible symptoms may not appear until years later. So it’s best to keep monitoring such a dog, and take into consideration all the other values from other thyroid tests.

In reality, the average pet owner is not going to ask for a TgAA test as part of annual bloodwork. But dogs intended to be used in breeding programs should have this measure on the record; it is one of the values that the Orthopedic Foundation for Animals (OFA) asks for when registering a dog in their database.

The diagnosis of “hypothyroidism” isn’t about a positive or a negative TgAA. But a positive or negative TgAA associated with hypothyroidism varies by breed. Hypothyroid English Setters and Golden Retrievers, for example, tend to test positive for TgAA more often than not, whereas hypothyroid Collies and Doberman Pinschers do not test positive for TgAA as often (Graham et. al, 624). Age at diagnosis was figured into those statistics somehow, which led researchers to suggest that the disease progresses differently, perhaps at a slower rate, in some breeds than in others. Overall, it’s about a 50/50 split across breeds whether you’re looking at autoimmune or idiopathic thyroiditis. You’ll have to consult the article or experts from your own breed club to see where your breed falls (there was no specific information for Shiba Inu, though Ferguson makes mentions the Basenji as one of the breeds with the highest prevalence of hypothyroidism based on some research done by Nachreiner at Michigan State University and others [649]).

This bit was interesting to me:

In a preliminary investigation of the influence of geography on the prevalence of thyroiditis in samples submitted to Michigan State University, some significant differences were observed. The prevalence of TgAA was significantly higher in samples submitted from North Dakota, Vermont, Wyoming, Minnesota, and Colorado compared with Michigan (range of odds ratios: 1.19 – 1.41; P < .05). The prevalence was significantly lower in samples from Massachusetts, Maryland, Virginia, North Carolina, Florida, South Carolina, Kentucky, Texas, West Virginia, Tennessee, and Alabama (range of odds ratios: 0.39 – 0.79; P < .05). There was no interaction with breed prevalence, but the underlying reasons (if any) for these observations have yet to be discovered. (Graham et. al, 623)

Tantalizing, isn’t it? Is it something in the water? Or the presence of puppy mills? Hunters? Urban sprawl? Mountain air? Who knows?!

At any rate, TgAA by itself is not an adequate test for diagnosing hypothyroidism. A dog can test positive for TgAA but still have T4 and fT4 levels within the normal range, which means the body is still producing enough hormone levels on its own, though the rumblings of worse to come are on the horizon. Likewise, a dog may not test positive for TgAA but the T4 and fT4 levels are low because the thyroids are already pooped; there’s nothing left worth attacking, so there’s no need to pump out more antibodies.

So I guess for the average pet owner like me, the TgAA was useful to suggest how far along Bowdu may have been in the disease. I’ll probably skip it next time, along with the T3 and fT3, and just order baseline readings of T4 and free T4 levels for the purposes of general monitoring.

Annotated list of References:
All articles come from The Thyroid special issue of Veterinary Clinics of North America: Small Animal Practice 37.4 (July 2007), edited by Cynthia R. Ward. I am disappointed to report that the veterinary college that delivered this title to my university library passed along a virtually pristine, unread copy. I sincerely hope that these articles are being accessed in electronic form by our future veterinary specialists in training!

• Graham, Peter A., Kent R. Refsal, Raymond F. Nachreiner. “Etiopathologic Findings of Canine Hypothyroidism.” Vet Clin Small Anim 37.4 (2007): 617-631.
  [too technical for me in some parts, and doesn’t really venture to offer any causes for the occurrence of thyroid disease though the authors tease their readers with intriguing statistics and suggestive avenues for further research; some illuminating charts which show some breed-specific information]
• Ferguson, Duncan C. “Testing for Hypothyroidism in Dogs.” Vet Clin Small Anim 37.4 (2007): 647-669.
  [clear, easy-to-understand survey of current available testing methods, their usefulness, limits, and attendant problems in diagnosis]
• Scott-Moncrieff, J. Catherine. “Clinical Signs and Concurrent Diseases of Hypothyroidism in Dogs and Cats.” Vet Clin Small Anim 37.4 (2007): 709-722.
  [also very technical, but covers a broad range and good for anyone who might be searching for answers on the relationship between thyroid disorders and other specific issues like cardiovascular and opthalmologic abnormalities, anemia, diabetes, bleeding disorders, etc.; good for mining additional sources]

Photo taken 3 February 2011

To bring this all back home, here are some pictures of Bowdu’s recent dermatological issues. He’s lost chunks of fur on his neck, one armpit, and a little bit on his belly, though he hasn’t been itching excessively nor does he seem to be in discomfort though he’s bald to the skin in some places, and there are patches of hyperpigmentation which come and go. We’re still monitoring him and treating him with medicated shampoo on affected areas, as well as Sulfodene on the hot spots, which seems to be keeping things from getting worse.

If this is just “allergies,” as I’m afraid the vet is going to say, then allergy season is really starting earlier and earlier each year… I’m still unwilling to admit that allergy season is year round, though this may be our punishment for living in the land of perpetual sunshine and no snow.

Shiba Inu & breed-specific profiles for aggression

Tags

aggression, akita, breeders, canine genetics, canine hypothyroidism, ethology, health tests, hemopet, shiba inu, thyroids, veterinary endocrinology, yukari takeuchi

I hope that breeders and those with any interest in behavioral issues in Nihon Ken are following and taking notice of Dr. Yukari Takeuchi’s work (武内　ゆかり, DVM, PhD). Takeuchi is at the University of Tokyo’s Laboratory of Ethology, and has done extensive research on genetic linkages and manifestations of aggression by breeds, with special attention to native Japanese breeds like the Akita and Shiba Inu.

In a 2006 report surveying a broad range of breeds, “A Comparison of the Behavioral Profiles of Purebred Dogs in Japan to Profiles of those in the United States and the United Kingdom,” Shiba were found to be ranked higher than average in aggressive behavior towards other dogs, watchdog barking, territorial defense, and snapping at children. They were clustered in a group known to have “high aggression, high reactivity, and medium trainability” along with the likes of Pomeranians, American Cocker Spaniels, Yorkshire Terriers, Irish Setters, Maltese, Pugs, Mini Schnauzers, Mini Dachshund, and others. The tag “medium trainability” says to me that Shibas may potentially have these unfavorable behaviors trained out of them, bringing home the point that socialization is key.

In another article from 2009, “Association analysis between canine behavioural traits in the Shiba Inu and genetic polymorphisms,” (Takeuchi Y, Kaneko F, Hashizume C, Masuda K, Ogata N, Maki T, Inoue-Murayama M, Hart BL, Mori Y, Animal Genetics 40: 616-622), what I understood was that there are tentative causal links between certain genes and Shiba aggression. However, because there are many social factors that contribute to aggression, as well as many ways to define aggression, more research needs to be done.

It was also noted that the Shibas surveyed were all from Japan, where many are still kept as watchdogs, particularly in rural areas. In such cases, certain types of “aggression” as noted in the 2006 study are favorably linked to their function.

In the meantime:

The reasons and motivations for having dogs vary from owner to owner; some want a watchdog for security while others desire a companion for family members. If veterinarians working at clinics know the behavioral profiles of purebred dogs and the tendencies in gender differences shown in this [2006] study, they can more appropriately advise prospective owners. This can facilitate a better quality of human-animal bond and perhaps prevent behavioral problems due to a mismatch between dogs and owners. In addition, veterinarians should inform potential owners of the importance of understanding the pedigree line within a breed, the behavior of the dam, sire, and siblings from previous litters, and the early environment during the socialization period, as has been repeatedly emphasized in previous studies (p. 7 of the 2006 study).

Takeuchi seems to consider veterinarian expertise the first line of defense against uninformed dog owners acquiring a potentially volatile breed. This statement stems from his methodology, wherein he asked veterinarians to answer based on their familiarity with the breeds surveyed, instead of breeders and purebred dog owners. In practice, I doubt most owners consult with a veterinarian before bringing home their dog; you usually get the dog first, then bring him to the vet. But his very efforts to find a genetic basis for aggression is intriguing nevertheless. If such a clear, direct genetic factor could be located, this would put a lot more weight on the selective breeding of purebred dogs, as well as throw open a whole set of related cultural issues on why breeders select for the temperaments and the individual dogs that they do.

I also find it interesting that a number of breeds considered to be “highly aggressive” also rank relatively highly on the Michigan State University’s charts for breeds at risk for thyroid disorders. Specifically, I’m looking at Maltese (#9, 16.5% autoimmune thyroiditis), Beagles (#10, 16.5%), Dalmatians (#11, 16.3%), Cocker Spaniels (#13, 15.7%), Irish Setters (#25, 12.6%), all grouped in the same cluster as Shiba Inu. In another cluster of dogs with “high aggression, low reactivity, high trainability,” there are breeds like the Boxer (#6, 18%.0), Great Dane (#36, 10.1%), Akita (#46, 8.6%), and Doberman Pinscher (#50, 8.4%). A lot of the smaller breeds rank pretty far down the list, like Yorkies and Pomeranians, which matches what I understand about hypothyroidism usually affecting medium to large-sized dogs.

But the notable overlaps make me wonder if a statistical correlation between breeds documented to be “aggressive” and thyroid disorders could be made even clearer by someone else with more rigorous analytical methods. While there is a lot of online and anecdotal information about hypothyroidism as an underlying factor contributing to aggression and behavioral changes in dogs (I’m thinking in particular about the work of Dr. Jean Dodds who presented her findings at the 1996 International Symposium on Canine Hypothyroidism), American DVMs seem to downplay the link between hypothyroidism and aggression, and there hasn’t been much published information in peer-reviewed journals echoing Jean Dodd’s findings.

Considering that 1996 wasn’t that long ago, in my mind, and that was the first (and only!) large-scale conference on canine hypothyroidism to have appeared in my searches, I bet more work can still be done. I just hope the specialists are talking to each other, and not content to let endocrinologists do their own thing, while ethologists do their own thing, and dermatologists and neurologists and hematologists and so forth are not limiting themselves to the information immediately at hand.

Heat, blood, moon

Tags

canine hypothyroidism, drugs, health tests, hemopet, soloxine, thyroids

I picked up Bowdu’s medication today — 0.2 mg of Levothyroxine (Soloxine), to be given twice daily. $24.70 for the first month’s dose of 60 pills, which buys me some time to track down a cheaper source, assuming he’s going to be on it for a longer duration. We’re to return for another blood draw in a month’s time. Given the near-impossibility of the last draw, I’m already looking into options to sedate Bowdu beforehand, though it’s probably not going to be pretty either way.

The numbers on his blood work do look pretty good. Everything falls neatly within the reference ranges. However, his thyroid readings looked like this:

T4
Results: 0.6 (LOW)
Reference Range: 1.0 – 4.0
Units: ug/dL

The Total T4 result is less than 1.0 mcg/dl. A Free-T4 by equilibrium dialysis may be helpful in supporting the diagnosis of hypothyroidism in patients demonstrating clinical signs compatible with hypothyroidism. Please use test code 7589 for this additional testing.

FREE T4 (Equilibrium Dialysis)
Results: 9.0
Reference Range 8 – 40
Units: PMOL/L

So there we have it.

I don’t have any doubts or major concerns about the readings, but I decided I still wanted another evaluation from an outside lab. I had asked for an extra vial of blood, which they pulled and I had kept stored on the condiment shelf of the refrigerator. Today I sent it via USPS Priority Mail to Hemopet/Hemolife. The FedEx receptionist whom I first tried to work with was exceptionally cranky and made me feel like a bioterrorist for not having the sample carefully wrapped by my vet. She seemed too freaked out that my vial of blood was going to spontaneously explode and infect everyone in the room with rabies, and couldn’t give me a clear answer on how to actually mail the damn thing, so I just sent it via USPS as Hemopet had originally recommended.

I ran some more errands, then came back to feed the dogs. As we were getting ready for our daily dog park run, I accidentally locked myself out of the house. How it happened was so ridiculous, I’m not even going into detail… Bowpi was on lead, with me, but Bowdu was stuck inside the house. Luckily, the Doggy Daddy was able to slip out of an evening commitment and reunite the pack, so we still got our daily dog park fill — complete with moonrise.

Thyroid test results

Tags

canine hypothyroidism, health tests, thyroids, vet

Thursday was kind of traumatic, and it wasn’t just because of the $500 vet bill. The entire visit took about an hour and a half. During our appointment (which ran much longer than anticipated), there was some tense conversation when we tried to ask for the thyroid tests to be done at an outside lab. Then, the first attempt at pulling a blood sample from our unsedated Shiba resulted in a noisy, violent, and shitty (literally) mess. Our vet returned to our examination room, obviously flustered and more or less ready to throw in the towel and pass us off onto their referred dermatologist. Bowdu, stinking of his own liquid feces, was returned to our room panting hard and sans cone. It was practically tossed into the room after him, then the door slammed with a note of disgust — his cone was the only thing that had saved a vet tech from getting seriously injured by our little monster. The fact that he had slipped out of it seemed to surprise the technician. Apparently we should have warned her about his Shiba ‘Scape Skillz, and not to handle him by the cone (he was wearing his Martingale on a leash, as well as the cone on a buckle collar stacked on top of it).

But we were there for a blood draw, so we were going to get it from him, dammit. After some quick thinking, we agreed to sedate him and go through with the procedure. Since the injection was just a jab to the hindquarters, my boyfriend was able to hold him in his arms while the job was done. Within a few minutes, Bowdu had collapsed into a woozy heap on the floor against my shoe. My boyfriend tried to pick him up off the floor, but apparently the urge to bite had not been sufficiently drugged out of him yet. Bowdu’s teeth clamped down hard on his hand, breaking skin. His muscles were all confused, and he didn’t seem capable of letting go by himself — my boyfriend had to pry his jaws apart with his free hand.

The vet tech’s professional timing was better. When they came to fetch him, all he could do to register his displeasure was stick his tongue out in a dopey-looking pout. The blood was collected, spun, and as of today, analyzed.

The good news is that Bowdu’s blood panel came back perfectly normal. Yay!

The better news is that his free T4 thyroid reading is low. The vet called it “borderline” low on the voice message left for me, but given that the “normal” range is between 8.0 and 40.0, and Bowdu’s reading was 9.0 (I don’t know the units yet, but I’ll find out later), I’m pretty confident in just calling it abnormally low and starting him on supplements ASAP.

This is “better” news because now we have a concrete step to take in improving his condition. One month after I started this blog, we’ve at least been able to get this far.

(Bow)Dues paid

Tags

canine hypothyroidism, cone of pride and triumph, cone of shame, health tests, vet

Here’s a summary of today:

• Exam / Consultation fee — $62.50
• Skin scraping (result: no mites) — $46.50
• Nursing/injections (quantity 2) — $34.50
• Dexmedetomid 0.5 mg/cc (doggy sedative) — $27.10
• Injectable Butorphanol (painkiller) — $23.62
• Senior Comprehensive bloodwork (SA090, includes Superchem, CBC, and T4, FT4 [ED] thyroid tests) — $230.85
• Enrofloxacin 68 mg (antibiotics, quantity 20) — $67.50
• Biohazard waste management — $4.99
• Nail trimming included — $0.00

TOTAL DUE: $497.56
TOTAL PAID: $497.56

We get our test results on Saturday. We’ll talk about details later.