NCL Golden Retriever Type
NCL Golden Retriever Type is a hereditary lysosomal storage disorder, which is a form of a bigger group of neurodegenerative disorders, known as the neuronal ceroid lipofuscinoses (NCLs). The NCLs cause accumulation of lipopigments in the body’s tissue, but they can be divided into different forms, based on the age of symptoms’ onset and genetic cause of the disorder. Based on the age of onset, NCLs can be classified as infantile (INCL), late-infantile, juvenile, and adult onset forms. Until now, several distinct mutations have been associated with different forms of NCL. The disorder has been identified in humans, cats, sheep, goats, monkeys, cattle etc.
Characteristics and Symptoms
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 Alzheimer’s and Parkinson’s disease. Abnormal accumulation of lipofuscin is the cause of the neuronal ceroid lipofuscinosis, causing progressive and permanent loss of motor and psychological ability.
Owners of affected Golden Retrievers recognize first symptoms when dogs are around 15 months of age or older. Symptoms include anxiety, constant circling, tremors, aggression, ataxia, localized and generalized seizures, and visual impairment.
NCL Golden Retriever Type is caused by a mutation in the CLN5 gene. The disorder is inherited as an autosomal recessive disorder. Dog carrying one copy of the mutated gene is heterozygous and will not show the NCL 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 NCL in Golden Retrievers.
Gilliam, D., Kolicheski, A., Johnson, GS, Mhlanga-Mutangadura, T., Taylor, JF., Schnabel RD, Katz ML. (2015) Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5. Mol Genet Metab. 115(2-3):101-9. doi: 10.1016/j.ymgme.2015.04.001. Epub 2015 Apr 23.