Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) in the cavalier King Charles spaniel

• What It Is
• Symptoms
• Diagnosis
• DNA Testing
• Treatment
• Breeders' Responsibilities
• What You Can Do
• Foods To Avoid
• Research News
• Related Links
• Veterinary Resources

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BOTTOM LINE: Cavaliers should not be fed any foods containing coconut oil or palm kernel oil or any other medium chain triglycerides (MCTs), unless (1) they have been tested and found to be clear or only a carrier of the mutated gene causing MCADD, or (2) they have been fed such MCT-foods for several months or years without having developed any seizures or other symptoms.

Medium chain triglycerides (MCTs) are fats derived mainly from coconut oil* and palm kernel oil. MCT oils have been found in some canine research studies to reduce seizure frequency in dogs diagnosed with idiopathic epilepsy. While some vendors of canine supplements claim MCT oils are of benefit to dogs diagnosed with mitral valve disease and/or dementia, there is no credible research evidence to support such marketing efforts.

Ketogenic diets**, which include adding MCTs to provide the medium chain fatty acids and ketone bodies as auxiliary brain energy, have been shown to be beneficial in treating epiletptic dogs. However, the cavalier King Charles spaniel, as a breed, is an exception to that general finding that MCTs are beneficial. Cavaliers affected with a gene mutation (described below) cannot digest MCTs, and they have been shown to be able to cause severe damage.

* Coconut oil, in particular, also is unhealthful for dogs for other well researched reasons. It contains a high percentage of long chain triglycerides (LCT) fatty acids as well as a high percentage of lauric acid, which behaves like a LCT even though classified as a MCT. Coconut oil also is over 90% saturated fatty acids. These ingredients are known to lead to inflammation and leaky gut syndrome in dogs, by increasing the amount of the endotoxin lipopolysaccharide (LPS) in the blood.
** Ketogenic diets are high in fat content (70% to 90% of total calories) and very low in carbohydrates (3% to 5% of total calories).

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What It Is

Medium-chain acyl-coenzyme A dehydrogenase is an enzyme found in coconut oil* and palm kernel oil, which is controlled by the ACADM gene. A protein-changing variant of the ACADM gene causes medium-chain acyl-coenzyme A dehydrogenase z9 deficiency (MCADD). This deficiency is a presumably inherited disorder (an organic aciduria) that prevents the dog's body from converting certain fats to energy, particularly medium-chain fatty acids and particularly during periods without food.

 MCADD prevents the affected dogs from digesting the fats as energy sources, particularly during times of fasting or increased metabolic demands. Affected dogs cannot burn fat for energy when their bodies run out of glucose, and as a result they may suffer from low blood sugar, central nervous system disfunctions, coma, or sudden death.

Fats are one of the three essential categories of food nutrients, the others being proteins and carbohydrates. CKCSs affected with MCADD cannot digest MCTs, and so when MCTs are the primary or sole source of fats in their diets, they digest no fats. In humans, MCADD has been found to lead to severe liver disorders, atrophy of the skeletal muscles, loss of consciousness, com a, and even sudden death.

Two published studies suggest that MCADD is fairly common among CKCSs. Recent statistical surveys indicate that about 10% of all cavaliers may be affected with MCADD and over half are carriers of the mutation. See the data periodically reported on the Facebook group page, "MCADD in the Cavalier King Charles Spaniel".

In a May 2007 article, veterinary neurologists report finding that a young cavalier, exhibiting seizures which were not controllable with anticonvulsants (potassium bromide, phenobarbital, and gabapentin), had an organic aciduria with excessively high urine excretion of hexanoylglycine. This is similar to medium-chain acyl-CoA dehydrogenase deficiency in humans.

In an October 2022 study of 162 cavaliers, researchers found that 52 of them were carriers of the protein changing variant of ACADM, and another 12 cavaliers were homozygous mutant dogs. That research was prompted by examination of a 3 year old, male neutered cavalier which displayed complex focal seizures and prolonged lethargy. The dog was found to have a single insertion deletion variant of ACADM causing the MCAD deficiency. The affected dog was treated with various dosages of levetiracetam and phenobarbital and was prescribed a low fat diet and a midnight snack consisting of carbohydrates. Prolonged periods of fasting and formulas that contained medium chain triglycerides as primary source of fat were also advised to avoid.

* Coconut oil, in particular, also is unhealthful for dogs for other well researched reasons. It contains a high percentage of long chain triglycerides (LCT) fatty acids as well as a high percentage of lauric acid, which behaves like a LCT even though classified as a MCT. Coconut oil also is over 90% saturated fatty acids. These ingredients are known to lead to inflammation and leaky gut syndrome in dogs, by increasing the amount of the endotoxin lipopolysaccharide (LPS) in the blood.

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Symptoms

In the reported veterinary journal cases, in which 164 cavaliers were studied, symptoms displayed by MCADD-affected dogs included recurrent and cluster seizures, complex focal seizures, and prolonged lethargy. These seizures may occur several times a week and last up to 24 hours each. Left untreated, symptoms could include severe liver disorders, atrophy of the skeletal muscles, loss of consciousness, coma, and sudden death.

Not all MCADD-affected dogs will be symptomatic, because they may not consume enough MCTs compared to other fats in their diets, or because they avoid lengthy fasting between meals. Nevertheless, since affected dogs cannot digest MCTs, there is no nutritional value in feeding MCTs to them.

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Diagnosis

Blood and urine testing shows organic aciduria with excessive excretion of hexanoylglycine, and increased medium-chain fatty acids. The clinical findings suggest a diagnosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) .

DNA testing will confirm the diagnosis, whether the affected dog is symptomatic or not.

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DNA Testing

• Genetic testing laboratories

Genetic testing laboratories offer a specific DNA test of the cavaliers’ saliva samples to detect whether the dogs have the mutation causing MCADD. The laboratories will send kits with swabs to the dogs' owners to obtain DNA samples from the dogs' mouths. Watch this YouTube video to learn how to properly use a swab to obtain DNA from your dog. See our Genetic Testing webpage for more information about DNA testing.

In this October 2022 article, the researchers suspected MCADD from the symptoms. They sequenced the genome of the affected cavalier and compared the data to 923 control genomes of different dog breeds. The ACADM gene encoding MCAD was considered the top functional candidate gene. The genetic analysis revealed a single homozygous private protein-changing variant in ACADM in the affected dog.  The current count of MCADD-affected cavaliers is 12%, and another 53% being carriers.

This variant, XM_038541645.1:c.444_445delinsGTTAATTCTCAATATTGTCTAAGAATTATG, introduces a premature stop codon and is predicted to result in truncation of ~63% of the wild type MCAD open reading frame, XP_038397573.1:p.(Thr150Ilefs*6). Targeted genotyping of the variant in 162 additional CKCSs revealed a variant allele frequency of 23.5% and twelve additional homozygous mutant dogs. The acylcarnitine C8/C12 ratio was elevated ~43.3 fold in homozygous mutant dogs as compared to homozygous wild type dogs.

Genetic testing laboratories which test for this mutation causing MCADD include:

• Canine Genetic Testing (CAGT), University of Cambridge Dept. of Veterinary Medicine
• GenSol Animal Diagnostics
• Laboklin

If a tested dog is affected, meaning it has a pair of the MCAD deficient genes, the report will look like this one:

This chart, below, shows what may be the expected offsprings of matings based upon the results of the MCT DNA test. While nature is not always this exact, the bottom three categories, breeding carriers and affecteds, aer the most likely to produce litters with affected offspring.

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Treatment

Seizures have been found to be very difficult to control with standard medications, including levetiracetam (Keppra, Elepsia, Spritam), potassium bromide, and phenobarbital, until feeding MCTs also has been discontinued.

Dietary treatment includes discontinuing feeding foods containing MCT oils (see this list below), and avoiding prolonged periods of fasting between meals. This means feeding snacks or treats between meals each day, such as just before bedtime.

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Breeders' Responsibilities

All breeders should have their cavalier breeding stock tested for the ACADM mutation before breeding.  Tests are available at Laboklin and Canine Genetic Testing and GenSol Animal Diagnostics.

The hazards of producing offspring with the ACADM mutation are that (a) being fed MCT oils and/or (b) being fasted, can lead to seizures and worse effects of this disorder. So, if cavaliers found to have the ACADM mutation are bred, its offspring should be DNA tested, and everyone involved (breeder, owner, veterinarian) needs to be aware that if an offspring dog has the mutation, it should not ever be fed any MCT oils and it should never be fasted.

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What You Can Do

All  cavalier owners should have their cavaliers tested for the ACADM mutation before feeding them any foods containing MCT oils. Tests are available at Laboklin and Canine Genetic Testing and GenSol Animal Diagnostics.

MCT oils, including coconut oil* and palm kernel oil, should not be fed to any cavalier unless that dog first has been tested and found to be clear or only a carrier of the ACADM mutation causing the MCAD-deficiency.

One possible exception to this general rule is that if the cavalier has been fed such foods containing MCTs for several months or longer without having developed any seizures or other symptoms, the owner might assume that the cavalier is not affected, on that trial-and-error basis. However, not all MCADD-affected dogs will display symptoms, because they may not consume enough MCTs compared to other fats in their diets, or because they avoid lengthy fasting between meals. Nevertheless, all MCADD-affected dogs, whether symptomatic or not, cannot digest MCTs.

Affected cavaliers must avoid these foods which have MCTs as their primary oils or fats:

• Coconut oil*, coconut glycerin, coconut milk, coconut meal, coconut meat, coconut flour
• Palm kernel oilbr>• Vegetable glycerin
• Goat's whole milk fat
• Cow's whole milk fat
• Butter
• Hard cheeses (especially cheddar, parmesan, gouda)
• Yogurt (some varieties, especially Greek)
• Ketogenic diets

Affected cavaliers must avoid the following dog foods (at least as sold in the USA), among others which contain MCTs. Be sure to check the ingredients lists on any other dog foods for coconut oil or coconut glycerin or coconut milk or coconut meat or coconut flour or palm kernel oil or MCT or "source of medium-chain triglycerides".

• Addiction Grain-Free Sensitive Care Limited Ingredient Diet (all varieties)
• All Provide Dog Gently Cooked Beef
• All Provide Dog Gently Cooked Pork
• All Provide Dog Gently Cooked Turkey
• All Provide Dog Raw Ready-to-Cook Beef
• All Provide Dog Raw Ready-to-Cook Pork
• All Provide Dog Raw Ready-to-Cook Puppy
• All Provide Dog Raw Ready-to-Cook Senior
• All Provide Dog Raw Ready-to-Cook Turkey
• All Provide Harvest Veggie Mix
• American Natural Premiun Market Fresh Legume-Free Fish Recipe
• Annamaet Ohana Grain-Free Puppy Formula
• Annamaet Original Senior Dog Food
• Annamaet Original Sensitive Skin & Stomach Dry Dog Food
• Annamaet Re-Juvenate Grain-Free Senior Formula
• Better Kibble for Dogs (all varieties)
• Bixbi Rawbble Dry Food for Dogs, Beef
• Bixbi Rawbble Dry Food for Dogs, Turkey
• Bixbi Rawbble Freeze-Dried for Dogs (some varieties)
• Bones & Co. Recipe Patties (all varieties)
• California Dog Kitchen Venison & Zucchini Recipe
• Castor & Pollux Organix Grain-Free (all varieties)
• Dave's Grain Free Countryside Blend
• Diamond Care Weight Management Formula for Adult Dogs
• Diamond Naturals (many varieties)
• Dr. Bob Goldstein's Wisdom Air-Dried Dog Food (all varieties)
• Dr. Harvey's Complete Meals (all varieties)
• Dylan's Pet Food (all varieties)
• Earth Animal Wisdom Air-Dried Recipes (all varieties)
• Edgard Cooper Fresh Organic Beef & Free-Range Turkey & Chicken
• Edgard Cooper Fresh Organic Free-Range Chicken
• Evanger’s Game Bird Recipe with Coconut Oil
• Evolve Classic Beef, Barley & Bison Recipe Dog Food
• Evolve Classic Lamb & Brown Rice Recipe Dog Food
• Farmina N&D Quinoa Skin & Coat (all varieties)
• Go! Solutions Sensitivities Limited Ingredient Duck Dry Dog Food
• Go! Solutions Sensitivities Limited Ingredient Lamb Dry Dog Food
• Go! Solutions Sensitivities Limited Ingredient Salmon Dry Dog Food
• Go! Solutions Sensitivities Limited Ingredient Turkey Dry Dog Food
• Green Juju Freeze-Dried Blend
• Green Juju Frozen Blends (all varieties)
• Happy Howies Meat Roll (all varieties)
• Happy Howies Pro Pack (all varieties)
• Health Extension Digestive Support (all varieties)
• Health Extension Gently Air Dried (all varieties)
• Health Extension Grain Free
• Health Extension Large Bites
• Health Extension Lite Chicken & Brown Rice Recipe
• Health Extension Original Chicken & Brown Rice Recipe
• Heart and Soil Grass-Fed Lamb & Spelt Recipe
• Heart and Soil Pasture-Raised Pork & Rye Recipe
• Hill's Prescription Diet Derm Complete
• Hill's Prescription Diet Metabolic
• Hill's Prescription Diet Metabolic + Mobility j/d
• Hill's Prescription Diet Mobility  j/d
• Hill's Prescription Diet c/d Multicare + Metabolic, Urinary +
• Hill's Prescription Diet ONC Care
• Hill's Prescription Diet Skin/Food Sensitivities d/d 
• Hill's Prescription Diet z/d Low Fat
• Hill's Science Diet Adult Perfect Weight
• Hill's Science Diet Perfect Weight & Joint Support
• Honest Kitchen Grain Free Beef Recipe
• Honest Kitchen Grain Free Chicken Recipe
• Honest Kitchen Grain Free Turkey Recipe
• Honest Kitchen Whole Grain Chicken & Oat Recipe
• I and Love and You Nude Super Food Grain-Free Red Meat Medley Dry Dog Food
• I and Love and You Nude Super Food Grain-Free Simply Sea Dry Dog Food
• Identity Dog Food (most varieties)
• Instinct Limited Ingredient Diet Grain-Free with Real Lamb
• Instinct Limited Ingredient Diet Grain-Free with Real Salmon
• Instinct Limited Ingredient Diet Grain-Free with Real Turkey
• Jinx Dog Kibble (all varieties)
• Just Food For Dogs Balanced Remedy
• Just Food For Dogs Joint & Skin Support Complete Meal
• Just Food For Dogs Veterinary Diet Hepatic Support
• Just Food For Dogs Veterinary Diet Critical Care Support
• Ketogenic Pet Foods (all varieties)
• Lucy Pet Vegetarian Formula Dog Food
• Lyka Fish Bowl
• Lyka Lamb Bowl
• Moochie Beauty Skin & Coat
• Moochie Grain Free Wet Dog Food
• Moochie Weight Control with Turkey
• Muenster Freeze-Dried Bites Free Range Elk Recipe
• Muenster Hunted and Gathered Chicken
• NAAVI Slow Roasted Bowl (all varieties)
• Nature's Diet Simply Raw Freeze-Dried Raw Whole Food Meal
• New Zealand Natural Pet Food Co. Woof (some varieties)
• Now Fresh Grain-Free Small Breed Adult Recipe Dry Dog Food
• Nutriment Enahancced Raw Diet Formula (all varieties)
• Nutriment Light Support
• Open Farm (all varieties)
• Organix Grain-Free (all varieties)
• OrgaNOMics Canned Dog Food (all varieties)
• Paw Foods Fresh Meals (all varieties)
• Pawstruck Air Dried Fish Recipe
• Pet Gourmet Lamb Oven Baked Kibble
• Pet Gourmet Turkey Oven Baked Kibble
• Pets Table Air-Dried Beef & Berries Recipe
• Pets Table Air-Dried Chicken & Sweet Potato Recipe
• Primal Freeze-Dried Nuggets
• Primal Kibble in the Raw (all varieties)
• Primal Pronto (all varieties)
• Primal Raw Frozen Nuggets
• Primal Raw Frozen Patties
• Primal Raw Frozen Pronto
• Purina One High Protein +Plus Vibrant Maturity
• Purina One +Plus Vibrant Maturity
• Purina Pro Plan Bright Mind
• Purina Pro Plan CC CardioCare
• Purina Pro Plan EN Gastroenteric
• Purina Pro Plan HA Hydrolyzed
• Purina Pro Plan Neurocare
• Purpose Freeze-Dried Raw Dog Food (most varieties)
• Raw Bistro Dehydrated Chicken
• Raw Bistro Dehydrated Turkey
• Raw Bistro Frozen Chicken
• Raw Bistro Frozen Turkey
• Raw Dynamic Freeze-Dried Beef Recipe
• Rayne Nutrition Ecoerm-BSFL Dry Dog Food
• Rayne Nutrition Low Fat Crocodilia MAINT Dry Dog Food
• Rayne Nutrition Low Fat Kangaroo MAINT Dry Dog Food (most varieties)
• Rayne Nutrition Plant-based Dry Dog Food
• Rayne Nutrition Low Fat Rabbit MAINT Dry Dog Food (most varieties)
• Rayne Nutrition Skin Relief Dry Dog Food
• Rockster Life-Enhancing Superfood Chickenrella
• Royal Canin Adult Selected Protein PD
• Royal Canin Adult Selected Protein PR
• Royal Canin Adult Hydrolyzed Protein PS
• Royal Canin Adult Selected Protein PW
• Royal Canin Adult Ultamino
• Royal Canin Diet Adult Vegetarian
• Royal Canin Veterinary Diet Adult Selected Protein PR Dry Dog Food
• Shine Pet Food Freeze Dried Raw Puppy Recipe
• Shine Pet Food Freeze Dried Raw Venison Recipe
• Shine Pet Food Frozen Raw Puppy Recipe
• Shine Pet Food Frozen Raw Rabbit Recipe
• Shine Pet Food Frozen Raw Venison Recipe
• Simple Food Project Bison Recipe
• Simple Food Project Lamb Recipe
• Smack Raw Dehydrated Super Food Caribbean-Salmon Fusion
• Smack Raw Dehydrated Super Food Rockin' Rockfish
• Small Batch Dog Lightly Cooked Batch (all varieties)
• Small Batch Pets Super Booster Freeze-Dried Bites (most varieties)
• Solid Gold Air Dried Beef Recipe
• Solid Gold Air Dried Chicken Recipe
• Sprankles' Freeze-dried Raw Dog Food Beef Recipe
• Sprankles' Freeze-dried Raw Dog Food Chicken Recipe
• Stashios Meal Appeal (all varieties)
• Steve's Real Food (all varieties)
• Vivus Smokey Maple Bacun Bites
• Volhard Dog Nutrition Rescue Diet
• Wet Noses Oven Baked Food for Dogs (all varieties)
• Wisdom Air-Dried Recipes (all varieties)
• X-Dog True Beast Freeze-Dried Raw Dog Food
• Yumwoof! Perfect Kibble (all varieties)
•• Yumwoof! Perfect Superfood (all varieties)

* Coconut oil, in particular, also is unhealthful for dogs for other well researched reasons. It contains a high percentage of long chain triglycerides (LCT) fatty acids as well as a high percentage of lauric acid, which behaves like a LCT even though classified as a MCT. Coconut oil also is over 90% saturated fatty acids. These ingredients are known to lead to inflammation and leaky gut syndrome in dogs, by increasing the amount of the endotoxin lipopolysaccharide (LPS) in the blood.

Consider joining the "MCADD in the Cavalier King Charles Spaniel" Facebook group.

Some affected dogs may not display symptoms because they either have not consumed enough MCTs or they have avoided prolonged fasting between meals. Nevertheless, since their bodies cannot digest MCTs, feeding them foods and/or supplements containing MCTs would be of no nutritional benefit.

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Research News

September 2023: Cavalier's epileptic seizures increased when fed Purina ProPlan NeuroCare for three months. In a September 2023 article, Japanese researchers (Kazumasa Nakatsuka, Brian Zanghi, Daisuke Hasegawa [right]) investigated the efficacy of Purina ProPlan NeuroCare, a dry (kibble) dog food "enriched" with medium-chain triglycerides (MCTs), on seizure frequency in seven dogs diagnosed with idiopathic epilepsy, including one cavalier King Charles spaniel, over  period of three months. The study was sponsored by Nestlé Purina Japan, and all investigators were employed or funded by Nestlé Purina Japan. They concluded overall that there was no significant difference in seizure frequency between the MCT-food and a placebo. However, they found that seizure activity increased in the CKCS while being fed the MCT-enriched food.

August 2023: August statistics of MCADD in cavaliers. In an August 29, 2023 post on the "MCADD in the Cavalier King Charles Spaniel" Facebook page, the reported DNA test results from the beginning of its record keeping in June 2023 through August 29 among 6 countries are:

• Tested cavaliers: 145
• Affected dogs: 14 (9.7%)
• Carrier dogs: 77 (53.1%)
• Clear dogs: 54 (37.2%)

October 2022: Over 39% of cavaliers have medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in a Swiss study. In an October 2022 Swiss study of 162 cavalier King Charles spaniels by Matthias Christen, Jos Bongers, Déborah Mathis, Vidhya Jagannathan, Rodrigo Gutierrez Quintana, and Tosso Leeb (right), they found that 52 of them were carriers of the protein changing variant of the ACADM gene, and another 12 cavaliers were homozygous mutant dogs. That research was prompted by examination of a 3 year old, male neutered cavalier which displayed complex focal seizures and prolonged lethargy. The dog was found to have a single insertion deletion variant of ACADM causing medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The affected dog was treated with various dosages of levetiracetam and phenobarbital and was prescribed a low fat diet and a midnight snack consisting of carbohydrates. Prolonged periods of fasting and formulas that contained medium chain triglycerides as primary source of fat were also advised to avoid.

May 2007: Cavalier appears to have medium-chain acyl-CoA dehydrogenase deficiency. In a May 2007 article, US and UK clinicians (Simon Platt [right], Yvonne L. McGrotty, Carley J. Abramson, Cornelis Jakobs) report a young cavalier King Charles spaniel having seizures over 12 months which could not be controlled by conventional anticonvulsants (potassium bromide, phenobarbital, and gabapentin) until levetiracetam. The dog had an organic aciduria and excessive urinary levels of hexanoylglycine, which was similar to humans with medium-chain acyl-CoA dehydrogenase deficiency.

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