NCL
(Canine Neuronal Ceroid Lipofuscinosis)
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The neuronal ceroid-lipofuscinoses (NCLs) are a class of inherited neurological disorders that have been
diagnosed in dogs, humans, cats, sheep, goats, cynomolgus monkeys, cattle, horses, and lovebirds. Among dogs,
NCL has been reported in many breeds, including English Setters, Tibetan Terriers,
American Bulldogs, Polish
Lowland Sheepdogs, Border Collies, Dalmatians, Miniature Schnauzers, Australian Shepherds, Australian Cattle Dogs,
Golden Retrievers, and other breeds (see list below). NCL is almost always inherited as an
autosomal recessive
trait
. In humans, mutations in one of at least six different genes can lead to NCL. Mutations in several other genes
have been found to be responsible for NCL in one or more animal species.

All of the NCLs have two things in common: pathological degenerative changes occur in the central nervous system,
and nerve cells accumulate material that is fluorescent when examined under blue or ultraviolet light. Although
neurological signs are always present in canine NCL, these signs vary substantially between breeds and can overlap
with signs present in other neurological disorders. Until the gene defect responsible for NCL has been identified for a
particular breed, a definitive diagnosis can only be made upon microscopic examination of nervous tissues at
necropsy.

Our goal is to identify the mutation responsible for NCL in each breed where NCL occurs so that the disease can be
diagnosed and carriers can be identified on the basis of a DNA-based test. To achieve this goal, we will first need to
identify dogs from each breed in which NCL has been definitively diagnosed based on presently available criteria. The
first step in identifying potentially affected dogs is for the owner or veterinarian to recognize signs that may be
indicative of NCL and bring these dogs to our attention. Toward this end, we list below the signs of NCL that have
been reported in the literature or observed in dogs we have examined in our clinics for each breed. Care should be
used in relying only on the listed disease signs as these may be based on very few cases and incomplete information.
In addition, it is theoretically possible for more than one form of NCL to exist within a particular breed.

NCL Description for American Bulldogs

Age of onset of clinical signs: 0.9 to 3 years

Age of death or euthanasia: 3.5 to 5.5 years

Abnormalities often observed by the owner:

Mental changes:
Physical symptoms may appear to worsen during times of stress. Affected dogs do not indicate
they are in any pain as coordination decreases.
Changes in gait and posture: Initially, uncoordinated movement in the rear is noted. As the disease progresses,
affected dogs develop a wide-based stance starting in rear, and eventually involving all four legs. Affected dogs may
exhibit muscle twitching, especially when sleeping. The dogs remain well-muscled through the course of the disease.
Visual abnormalities: None reported
Seizures/convulsions: None reported
Other changes: None reported

Abnormalities observed upon clinical examinations:

Clinical neurologic changes:
Progressive ataxia and hypermetria is present in all four limbs, but more pronounced
in the pelvic limbs. Conscious proprioception and hopping reactions are delayed in the pelvic limbs but normal in the
forelimbs on initial examination. In advanced stages conscious proprioception reactions are absent in all four limbs
and dogs have difficulty rising from a recumbent position without assistance. A wide-based stance of the pelvic limbs is
observed in younger affected dogs; this progresses to a wide-based stance of all four limbs at later examinations.
Spinal reflexes and cranial nerve examinations are normal. The dogs remain well muscled.
Clinical ophthalmic changes: None reported
Visual abnormalities: None reported
Retinal changes: None reported
Electroretinography (ERG): None reported
Other clinical findings: None reported


Mode of inheritance:
Autosomal recessive.

Gene containing mutation: The causative mutation has been identified and a DNA test is now available. See details at
http://www.caninegeneticdiseases.net/CL_site/formsCL.htm

References:
Evans J, Katz ML, Levesque D, Shelton D, deLahunta A and O’Brien DP: A Variant Form of Neuronal Ceroid
Lipofuscinosis in American Bulldogs (2005) J. Vet. Internal Med., 19:44-51.

This info is from the
CANINE GENETIC DISEASES NETWORK


CLICK HERE
Autosomal Recessive Gene Info