What is Neuronal Canine Ceroid Lipofuscinosis Basics (NCL)
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, Dachshunds, 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.
A mutation in CTSD is responsible for NCL in American Bulldogs.
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 in the 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
Brain: The entire external surface of the brain has a light brown hue but no evidence of cortical atrophy. Microscopically, PAS-positive storage material is present in cerebral cortex, brainstem, and cerebellum. The storage material in all cells exhibits a goldenyellow autofluorescence. Axonal spheroids are present in the brain and spinal cord. Ultrastructurally, storage bodies consist of membrane-bound organelles with crosssectional diameters generally ranging from 0.5 to 3 microns. The inclusion body profiles are sometimes round but more often irregular. The bulk of the storage body contents are coarsely granular and most storage bodies contain numbers of somewhat spherical aggregates of the granular material. In addition, storage bodies from all 3 cell types contain well-delineated spherical dark-staining inclusions that are mostly smaller than 0.1 microns in diameter. In some cells in and near the Purkinje cell layer of the cerebellum, the perinuclear cytoplasm is filled with storage material that appears to be an aggregation of smaller storage bodies that have fused.
Eyes: Microscopically, PAS-positive storage material is present in ganglion cells of the retina. Under electron microscopic examination, the storage bodies in retinal ganglion cells have an additional ultrastructural feature of lighter-staining spherical inclusions with the relatively uniform electron density typical of lipid droplets.
Other organs and structures: None noted
Mode of inheritance: Autosomal recessive.
Resource: Canine Genetic Diseases