There are several
documented lysosomal storage diseases. Neuronal ceroid-lipofuscinosis
(NCL) referred to in humans as Battens disease has been most commonly
reported in the dog. A similar condition affects cats. The
disease results from intraneuronal accumulations of ceroid-lipofuscin
granules. It has been related to primary cerebellar disease in the dog
and can result in cerebellar atrophy. Neuronal ceroid
lipofuscinosis is a type of inherited lysosomal storage disorder that
results in accumulation of lysosomal storage bodies in the cells of
many tissues of the affected animal. This leads to progressive
neurodegeneration (degeneration of brain and eye cells) and results in
severe neurological impairment and early death. Storage diseases
can primarily affect the cerebellum, but they usually affect multiple
areas of the brain and spinal cord. Affected dogs appear normal
at birth, but begin to exhibit symptoms early in life – around 1- 2
years of age however, they may not show clinical signs until they
mature.. The age of onset and severity of the disease varies greatly
among individuals.
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.
Symptoms can
include visual abnormalities, rapid changes in vision including
blindness, bumping into objects, confusion, aimless wandering, loss of
memory for learned tasks, trembling episodes, behaviour changes and
circling. The disease progresses over 2-3 years to include poor
movement incoordination, difficulty in swallowing, vision and hearing
loss, rapid motion of the eyeball (nystagmus), voice changes.
Enlargement of the nerves of the forelimbs can be detected, which is
due both to fluid accumulation and infiltration of the nerves. At a
later stage, signs of the disease include seizures, tremors, and gait
abnormalities. Visual impairment may occur. Due to the severity
of the disease, affected dogs rarely survive beyond 26-28 months.
Diagnosis of
ceroid lipofuscinosis is based upon clinical signs, especially in a
susceptible breed. Cerebrospinal fluid analysis is usually normal but
may reveal increased protein levels with a normal cell count. Computed
tomographic (CAT) or magnetic resonance imaging (MRI) of the brain of
dogs with ceroid lipofuscinosis may reveal abnormalities, such as brain
atrophy and abnormal brain-tissue density. Definitive diagnosis will
require additional skin and/or blood tests.
There is no
treatment or cure at this time. Prognosis for Ceroid
Lipofuscinosis is grave. For the majority of these disorders, affected
animals are euthanized due to progressive worsening neurological
dysfunction within the first year of life. For the more slowly
progressive disorders (ceroid lipofuscinosis), continuous neurologic
dysfunction leads to death or euthanasia usually within 1-2 years of
diagnosis. Despite the poor outlook for these disorders, bone marrow
transplantation and lysosomal enzyme replacement therapy have been
successful in some human and animal cases. Gene transfer therapy is
also being actively investigated and will hopefully be available in the
future.
References:
1. Genetic Aberrancies and Neurodegenerative Disorders (Advances in
Cell Aging and Gerontology) by M.P. Mattson
2. A Practical Guide to Canine and Feline Neurology by Curtis W. Dewey
