Cerebellar abiotrophy
Encyclopedia
Cerebellar abiotrophy also referred to as the cerebellar cortical abiotrophy (CCA), which is a genetic
neurological
disease in animals best known to affect certain breeds of horse
s and dog
s. It develops when the neuron
s known as Purkinje cell
s, located in the cerebellum
of the brain
, begin to die off. These cells affect balance and coordination. They have a critical role to play in the brain. The Purkinje layer allows communication between the granular and molecular cortical layers in the cerebellum. Put simply, without Purkinje cells, an animal loses its sense of space and distance, making balance and coordination difficult.
Abiotrophy means the loss of a vital nutritive
factor. The exact cause of cerebellar abiotrophy is not known, but it is thought to be due to an intrinsic
metabolic defect.
In most cases, the Purkinje neurons
begin to die off shortly after the animal is born and the condition is noticeable when the animal is less than six months old, though sometimes the onset of symptoms is gradual and the animal is much older before the owner or caretaker notices a problem.
CA cannot be prevented, other than by selective breeding to avoid the gene, and it cannot be cured. Genetic testing can detect carriers. In addition to dogs and horses, there also have been cases of cerebellar abiotrophy in Siamese
and Domestic shorthair cat
s; in Angus
, Polled Hereford, Charolais
and Holstein Friesian
cattle
; Merino
and Wiltshire sheep; and Yorkshire
pig
s.
s is sometimes called progressive neuronal abiotrophy (PNA). Other terms used to describe the condition in dogs include cerebellar cortical atrophy and postnatal cerebellar cortical degeneration.
Cerebellar abiotrophy in horses was originally thought to be a form of cerebellar hypoplasia
and was described as such in older research literature. However, it was discovered that in horses, the die-off of purkinje cells began after the animal was born, rather than occurring in utero
. Cerebellar hypoplasia is particularly common in cat
s and has similar symptoms.
There are other diseases that lead to cerebellar degeneration, but the loss of Purkinje cells is a clear way to diagnose CA, and the combination of symptoms is sufficiently unique that CA can easily be distinguished from other conditions, even in a living animal.
Symptoms of cerebellar abiotrophy include ataxia
or lack of balance, an awkward wide-legged stance, a head tremor (intention tremor) (in dogs, body tremors also occur), hyperreactivity, lack of menace reflex, stiff or high-stepping gait
, coarse or jerky head bob when in motion (or in very young animals, when attempting to nurse), apparent lack of awareness of where the feet are (sometimes standing or trying to walk with a foot knuckled over), poor depth perception, and a general inability to determine space and distance. The symptoms are, when taken as a group, fairly unique and not easily mimicked by other illnesses, though certain types of neurological injury and infection do need to be ruled out. Verifying the diagnosis in a laboratory setting is only possible by examining the brain
post-mortem to determine if there has been a loss of Purkinje cells.
Most affected animals have normal intelligence and mildly affected animals can, in theory, live out a normal lifespan. However, affected animals are quite accident-prone, and for this reason many animals that develop CA, particularly horses, are euthanized for humane reasons. Horses may experience difficulty stepping up and over objects, run into fences, fall easily, and even if allowed to mature to full growth, are generally considered unsafe to ride. Dogs may need lifetime assistance with tasks such as climbing stairs.
In horses, the symptoms may worsen from the time of onset for six to 12 months, but if not severe enough to mandate euthansia, they stabilize over time. In some dog breeds, symptoms appear to progressively worsen, but research is not consistent on this point. There also is some evidence that affected animals partially compensate for the condition by cognitively learning alternative methods for moving or to determine distance, and thus appear to improve because they become less accident-prone.
s. It has also been observed in the Miniature horse
, the Gotland Pony
, one Eriskay Pony
, and possibly the Oldenburg
. Most foals appear normal at birth, with symptoms noticeable at an average age of four months, though there have been cases where the condition is first seen shortly after birth and other cases where symptoms are first recognized in horses over one year of age.
In horses, CA is believed to be linked to an autosomal
recessive gene. This means it is not sex-linked, and the allele has to be carried and passed on by both parents in order for an affected animal to be born. Horses that only carry one copy of the gene may pass it on to their offspring, but themselves are perfectly healthy—without symptoms of the disease. Because it is recessive, the allele for CA may pass through multiple generations before it is expressed.
CA is sometimes misdiagnosed. Though the symptoms are quite distinguishable from other neurological conditions, it has been confused with Wobbler's syndome
, Equine Protozoal Myeloencephalitis
(EPM), and injury-related problems such as a concussion.
A DNA test which identifies markers associated with cerebellar abiotrophy is available. The test has been refined to identify the most likely mutations, and retesting of earlier samples based on an earlier indirect marker test developed by UCD, indicated a 97% accuracy rate for the old test relative to the newer version, with no false negatives. Continued research is taking place at the Veterinary Genetics Laboratory at the UC Davis School of Veterinary Medicine
. Researchers working on this problem include Dr. Cecilia Penedo, PhD, and Leah Brault, PhD. The late Dr. Ann Bowling also made significant contributions to the genetics
research on CA.
, Gordon Setter
, Border Collie
, Labrador Retriever
, Airedale
, English Pointer
, Scottish Terrier
, Kerry Blue Terrier
, Miniature Schnauzer
, and other dog
breeds. Time of onset varies. In a few breeds, such as the Beagle
, Rough Collie
, and Miniature Poodle, Purkinje cells begin to die off at or shortly before birth, and pups are born with symptoms or develop symptoms by three to four weeks of age. Most breeds prone to the condition, such as the Kerry Blue Terrier, Border Collie, Australian Kelpie, and Labrador Retriever, begin showing symptoms between six and sixteen weeks of age. In a very few breeds, such as the American Staffordshire Terrier
, Old English Sheepdog
, Brittany Spaniel, and Gordon Setter, symptoms do not appear until adulthood or even middle age.
In dogs, CA is also usually an autosomal recessive gene, but in a few breeds, such as the English Pointer
, the gene is sex-linked
.
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
neurological
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
disease in animals best known to affect certain breeds of horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s and dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s. It develops when the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s known as Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s, located in the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, begin to die off. These cells affect balance and coordination. They have a critical role to play in the brain. The Purkinje layer allows communication between the granular and molecular cortical layers in the cerebellum. Put simply, without Purkinje cells, an animal loses its sense of space and distance, making balance and coordination difficult.
Abiotrophy means the loss of a vital nutritive
Nutrition
Nutrition is the provision, to cells and organisms, of the materials necessary to support life. Many common health problems can be prevented or alleviated with a healthy diet....
factor. The exact cause of cerebellar abiotrophy is not known, but it is thought to be due to an intrinsic
Intrinsic and extrinsic properties
An intrinsic property is an essential or inherent property of a system or of a material itself or within. It is independent of how much of the material is present and is independent of the form the material, e.g., one large piece or a collection of smaller pieces...
metabolic defect.
In most cases, the Purkinje neurons
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
begin to die off shortly after the animal is born and the condition is noticeable when the animal is less than six months old, though sometimes the onset of symptoms is gradual and the animal is much older before the owner or caretaker notices a problem.
CA cannot be prevented, other than by selective breeding to avoid the gene, and it cannot be cured. Genetic testing can detect carriers. In addition to dogs and horses, there also have been cases of cerebellar abiotrophy in Siamese
Siamese (cat)
The Siamese is one of the first distinctly recognized breeds of Oriental cat. The origins of the breed are unknown, but it is believed to be from Thailand. In Thailand, where they are one of several native breeds, they are called Wichian Mat...
and Domestic shorthair cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s; in Angus
Angus cattle
Angus cattle are a breed of cattle much used in beef production. They were developed from cattle native to the counties of Aberdeenshire and Angus in Scotland, and are known as Aberdeen Angus in most parts of the world....
, Polled Hereford, Charolais
Charolais cattle
Charolais cattle are a beef breed of cattle which originated in Charolais, around Charolles, in France. They are raised for their meat and are known for their composite qualities when crossed with other breeds, most notably Angus and Hereford cattle...
and Holstein Friesian
Holstein (cattle)
Holstein cattle is a breed of cattle known today as the world's highest production dairy animal. Originating in Europe, Holsteins were bred in what is now the Netherlands and more specifically in the two northern provinces of North Holland and Friesland...
cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...
; Merino
Merino
The Merino is an economically influential breed of sheep prized for its wool. Merinos are regarded as having some of the finest and softest wool of any sheep...
and Wiltshire sheep; and Yorkshire
American Yorkshire pig
The American Yorkshire, a breed of domestic pig, is the American version of the Yorkshire pig , white in color, with erect ears, and the most recorded swine breed in the United States....
pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s.
Other terms used
The condition in Kerry Blue TerrierKerry Blue Terrier
The Kerry Blue Terrier is a breed of dog. Mistakenly thought to be from County Kerry in South West Ireland, it's actually from Tipperary in South Central Ireland. In Ireland it is often called the Irish Blue Terrier...
s is sometimes called progressive neuronal abiotrophy (PNA). Other terms used to describe the condition in dogs include cerebellar cortical atrophy and postnatal cerebellar cortical degeneration.
Cerebellar abiotrophy in horses was originally thought to be a form of cerebellar hypoplasia
Cerebellar hypoplasia (non-human)
Cerebellar hypoplasia is a disorder found in cats and dogs in which the cerebellum is not completely mature at birth.-Symptoms:Usually symptoms of cerebellar hypoplasia can be seen immediately at birth in cats, but sometimes can take two months or so to become apparent in dogs. Cerebellar...
and was described as such in older research literature. However, it was discovered that in horses, the die-off of purkinje cells began after the animal was born, rather than occurring in utero
In utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
. Cerebellar hypoplasia is particularly common in cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s and has similar symptoms.
There are other diseases that lead to cerebellar degeneration, but the loss of Purkinje cells is a clear way to diagnose CA, and the combination of symptoms is sufficiently unique that CA can easily be distinguished from other conditions, even in a living animal.
Symptoms
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
or lack of balance, an awkward wide-legged stance, a head tremor (intention tremor) (in dogs, body tremors also occur), hyperreactivity, lack of menace reflex, stiff or high-stepping gait
Horse gait
Horse gaits are the various ways in which a horse can move, either naturally or as a result of specialized training by humans.-Classification:...
, coarse or jerky head bob when in motion (or in very young animals, when attempting to nurse), apparent lack of awareness of where the feet are (sometimes standing or trying to walk with a foot knuckled over), poor depth perception, and a general inability to determine space and distance. The symptoms are, when taken as a group, fairly unique and not easily mimicked by other illnesses, though certain types of neurological injury and infection do need to be ruled out. Verifying the diagnosis in a laboratory setting is only possible by examining the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
post-mortem to determine if there has been a loss of Purkinje cells.
Most affected animals have normal intelligence and mildly affected animals can, in theory, live out a normal lifespan. However, affected animals are quite accident-prone, and for this reason many animals that develop CA, particularly horses, are euthanized for humane reasons. Horses may experience difficulty stepping up and over objects, run into fences, fall easily, and even if allowed to mature to full growth, are generally considered unsafe to ride. Dogs may need lifetime assistance with tasks such as climbing stairs.
In horses, the symptoms may worsen from the time of onset for six to 12 months, but if not severe enough to mandate euthansia, they stabilize over time. In some dog breeds, symptoms appear to progressively worsen, but research is not consistent on this point. There also is some evidence that affected animals partially compensate for the condition by cognitively learning alternative methods for moving or to determine distance, and thus appear to improve because they become less accident-prone.
Cerebellar abiotrophy in horses
Cerebellar abiotrophy (CA) is best known as a condition affecting Arabian horseArabian horse
The Arabian or Arab horse is a breed of horse that originated on the Arabian Peninsula. With a distinctive head shape and high tail carriage, the Arabian is one of the most easily recognizable horse breeds in the world. It is also one of the oldest breeds, with archaeological evidence of horses...
s. It has also been observed in the Miniature horse
Miniature horse
Miniature horses are found in many nations, particularly in Europe and the Americas. The designation of miniature horse is determined by the height of the animal, which, depending on the particular breed registry involved, is usually less than as measured at the last hairs of the mane, which are...
, the Gotland Pony
Gotland Pony
-External links:**...
, one Eriskay Pony
Eriskay pony
The Eriskay Pony is a breed of pony from Scotland. It is generally grey in colour, and has a dense, waterproof coat that protects it in harsh weather. The breed developed in ancient times in the Hebrides islands in Scotland, and a small population remained pure and protected from crossbreeding by...
, and possibly the Oldenburg
Oldenburg (horse)
The Oldenburg is a warmblood horse from the north-western corner of Lower Saxony, what was formerly the Grand Duchy of Oldenburg. The breed was built on a mare base of all-purpose farm and carriage horses, today called the Alt-Oldenburger...
. Most foals appear normal at birth, with symptoms noticeable at an average age of four months, though there have been cases where the condition is first seen shortly after birth and other cases where symptoms are first recognized in horses over one year of age.
In horses, CA is believed to be linked to an autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive gene. This means it is not sex-linked, and the allele has to be carried and passed on by both parents in order for an affected animal to be born. Horses that only carry one copy of the gene may pass it on to their offspring, but themselves are perfectly healthy—without symptoms of the disease. Because it is recessive, the allele for CA may pass through multiple generations before it is expressed.
CA is sometimes misdiagnosed. Though the symptoms are quite distinguishable from other neurological conditions, it has been confused with Wobbler's syndome
Wobbler disease
Wobbler disease is a condition of the cervical vertebrae that causes an unsteady gait and weakness in dogs and horses. The term wobbler disease refers to a number of different conditions of the cervical spinal column that all cause similar symptoms...
, Equine Protozoal Myeloencephalitis
Equine Protozoal Myeloencephalitis
Equine protozoal myeloencephalitis, or EPM, is a disease cause by a protozoal infection of the central nervous system of horses.-History:...
(EPM), and injury-related problems such as a concussion.
A DNA test which identifies markers associated with cerebellar abiotrophy is available. The test has been refined to identify the most likely mutations, and retesting of earlier samples based on an earlier indirect marker test developed by UCD, indicated a 97% accuracy rate for the old test relative to the newer version, with no false negatives. Continued research is taking place at the Veterinary Genetics Laboratory at the UC Davis School of Veterinary Medicine
UC Davis School of Veterinary Medicine
The University of California, Davis, School of Veterinary Medicine, is the largest veterinary school in the United States. Established in 1948, the school is the primary health resource for California's various animal populations. The school is ranked 2nd for veterinary schools in the country...
. Researchers working on this problem include Dr. Cecilia Penedo, PhD, and Leah Brault, PhD. The late Dr. Ann Bowling also made significant contributions to the genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
research on CA.
Cerebellar abiotrophy in dogs
CA has been seen in the Australian KelpieAustralian Kelpie
The Kelpie is an Australian sheep dog successful at mustering and droving with little or no command guidance. They are medium-sized dogs and come in a variety of colours...
, Gordon Setter
Gordon Setter
A Gordon Setter is a large breed of dog, a member of the setter family that also includes both the better-known Irish Setter and the English Setter. Setter breeds are classified as members of either the Sporting or Gundog Group depending on the national kennel club or council. The original purpose...
, Border Collie
Border Collie
The Border Collie is a herding dog breed developed in the Anglo-Scottish border region for herding livestock, especially sheep. It is the most widespread of the collie breeds....
, Labrador Retriever
Labrador Retriever
The Labrador Retriever is one of several kinds of retriever, a type of gun dog. A breed characteristic is webbed paws for swimming, useful for the breed's original purpose of retrieving fishing nets. The Labrador is the most popular breed of dog by registered ownership in Canada, the United...
, Airedale
Airedale
Airedale is a geographic area in Yorkshire, England, corresponding to the river valley of the River Aire . The valley stretches from the river's origin in Malham which is in the Yorkshire Dales, down past Keighley and Bingley, through Leeds and Castleford and on to join the Humber...
, English Pointer
Pointer (dog breed)
The Pointer, often called the English Pointer, is a breed of dog developed as a gun dog. It is one of several pointing breeds.-Appearance:...
, Scottish Terrier
Scottish Terrier
The Scottish Terrier , popularly called the Scottie, is a breed of dog. Initially one of the highland breeds of Terrier that were grouped under the name of Skye Terrier, it is one of five breeds of terrier that originated in Scotland, the other four being the modern Skye, Cairn, Dandie Dinmont, and...
, Kerry Blue Terrier
Kerry Blue Terrier
The Kerry Blue Terrier is a breed of dog. Mistakenly thought to be from County Kerry in South West Ireland, it's actually from Tipperary in South Central Ireland. In Ireland it is often called the Irish Blue Terrier...
, Miniature Schnauzer
Miniature Schnauzer
The Miniature Schnauzer is a breed of small dog of the Schnauzer type that originated in Germany in the mid-to-late 19th century. Miniature Schnauzers developed from crosses between the Standard Schnauzer and one or more smaller breeds such as the Poodle and Affenpinscher.The breed remains one of...
, and other dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
breeds. Time of onset varies. In a few breeds, such as the Beagle
Beagle
The Beagle is a breed of small to medium-sized dog. A member of the Hound Group, it is similar in appearance to the Foxhound, but smaller, with shorter legs and longer, softer ears. Beagles are scent hounds, developed primarily for tracking hare, rabbit, and other game...
, Rough Collie
Rough Collie
The Rough Collie is a long coated breed of medium to large size dog that in its original form was a type of collie used and bred for herding in Scotland. Originating in the 1800's, it is now well known through the works of author Albert Payson Terhune, and through the Lassie novel, movies, and...
, and Miniature Poodle, Purkinje cells begin to die off at or shortly before birth, and pups are born with symptoms or develop symptoms by three to four weeks of age. Most breeds prone to the condition, such as the Kerry Blue Terrier, Border Collie, Australian Kelpie, and Labrador Retriever, begin showing symptoms between six and sixteen weeks of age. In a very few breeds, such as the American Staffordshire Terrier
American Staffordshire Terrier
The American Staffordshire terrier is a medium-sized, short-coated American dog breed. In the early part of the twentieth century the breed gained social stature and was accepted by the American Kennel Club as the American Staffordshire Terrier in 1936...
, Old English Sheepdog
Old English Sheepdog
The Old English Sheepdog is a large breed of dog which was developed in England from early herding types of dog. The Old English Sheepdog has very long fur covering the face and eyes...
, Brittany Spaniel, and Gordon Setter, symptoms do not appear until adulthood or even middle age.
In dogs, CA is also usually an autosomal recessive gene, but in a few breeds, such as the English Pointer
Pointer (dog breed)
The Pointer, often called the English Pointer, is a breed of dog developed as a gun dog. It is one of several pointing breeds.-Appearance:...
, the gene is sex-linked
Sex linkage
Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...
.
CA in horses
- "Genetic Diseases." Arabian Horse Association
- "Cerebellar Abiotrophy," Fact sheet, UC Davis Veterinary Genetics Laboratory.
- Goodwin-Campiglio, Lisa. "Cerebellar Abiotrophy." F.O.A.L., accessed November 6, 2011.
- Johnson, Robert S. "Test Allows Arabian Breeders to Scan for Inherited Neurologic Disorder" The Horse online edition, September 23 2008, Article # 12746. Accessed September 23, 2008
- Penedo, M. Cecilia T. and Leah Brault. "Progress Toward Identifying the Gene Responsible for Equine Cerebellar Abiotrophy (CA)." Genetics, Research Review, 2006, Center for Equine Health, University of California, Davis. Accessed November 6, 2011
- Sponseller, Brett A. A Pedigree Analysis of Cerebellar Cortical Abiotrophy in the Arabian Horse. (Fourth-year seminar paper). Ithaca, NY: College of Veterinary Medicine, Cornell University, 1994.
- WAHO. "GENETIC DISORDERS IN ARABIAN HORSES: CURRENT RESEARCH PROJECTS." World Arabian Horse Association, accessed online October 23, 2007
CA in dogs
External links to information on CA in Horses
- A composite Site for information on Cerebellar Abiotrophy (CA)with CA Status List of Disclosed Horses.
- Information from the University of California-Davis on Cerebellar Abiotrophy in horses
- F.O.A.L., an organization dedicated to fighting lethal genetic conditions in Arabian horses.
- . The Dr. Van Haeringen Laboratorium bv, The Netherlands for CA testing in Europe. English and Dutch.