Neuronal Ceroid Lipofuscinosis – NCL 1 Dachshund Type
NCL 1 Dachshund type is a form of neuronal ceroid lipofuscinoses. The neuronal ceroid lipofuscinoses (NCLs) are a group of hereditary neurological disorders known to affect humans, cats, sheep, goats, monkey, cattle etc. The neuronal ceroid lipofuscinoses (NCLs) are divided into genetically distinct forms, all causing accumulation of lipopigments in the body’s tissue. To date NCLs have been associated with 8 different genetic mutations. Another classification of NCLs includes age of onset, so they are divided into infantile (INCL), late-infantile, juvenile and adult onset forms. First time Neuronal Ceroid Lipofuscinosis Dachshund Type (NCL 1) was described in a Wire-haired Dachshund in 1977. Since then, NCL 1 was reported several times in the Dachshund breed.
Lipofuscin is a yellow to brown lipopigment composed of residues of lysosomal digestion. It is considered to be one of the aging pigments localized in the liver, kidney, heart muscle, retina, nerve cells and ganglion cells. Lipofuscin in high levels causes membrane damage, damage to mitochondria and lysosomes. Its balance within the cell is realized via formation and disposal mechanisms. When this balance is disrupted, accumulation of lipofuscin occurs. In humans, this condition is related to several diseases, such as degenerative disease of the eye, the macular degeneration and inherited juvenile form of macular degeneration, the Stargardt disease, as well the Alzheimer’s, Parkinson’s disease etc. Abnormal accumulation of lipofuscin is cause of the neuronal ceroid lipofuscinosis, causing progressive and permanent loss of motor and psychological ability.
Characteristics and Symptoms
Neuronal Ceroid Lipofuscinosis affected Dachshunds start to exhibit first symptoms around 9 months of age, such as kyphosis, stiffness of gait, lack of muscle coordination and difficulties in balancing and jumping. The symptoms progress during following months and uncontrolled rhythmic head movements, ataxia and general weakness will develop. Affected dogs also shows behavioral changes, such as increased nervousness, decreased interactions with other dogs, severe dementia, sensitivity to loud noises, circling behavior and increased inappropriate vocalization. Eye examination reveals diffuse retinal thinning and severe retinal vessel degeneration. Eye disorder progresses until complete blindness. Microscopy shows heavy accumulation of autofluorescent storage material, lipofuscin, in neurons of the retina, cerebellum and cerebral cortex.
Due to severity and progressive nature of NCL1, affected dogs are usually euthanized by their owners due to humane reasons.
NCL 1 Dachshund Type is caused by an insertion mutation within intron 5 of PPT1 gene. The PPT1 gene is encoding for the enzyme palmitoyl protein thioesterase 1 (PPT1). This enzyme catalyzes the removal of specific acyl groups from proteins or peptides during lysosomal degradation, and in this way participates in certain protein breakdown. The mutation causes expression of malfunctional enzyme, resulting in accumulation of these molecules in cells and NCL symptoms.
Neuronal Ceroid Lipofuscinosis Dachshund Type (NCL 1)is inherited as an autosomal recessive disorder. Dog carrying one copy of the mutated gene is heterozygous and will not show the NCL1 symptoms. When mating two carriers (heterozygotes) at conception each cub has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Currently there is no cure for NCL1.
Sanders DN, Farias FH, Johnson GS, Chiang V, Cook JR, O’Brien DP, Hofmann SL, Lu JY, Katz ML. A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund. Mol Genet Metab. 2010 Aug; 100(4):349-56.