Neuronal Canine Ceroid Lipofuscinosis Basics

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.

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, more than one form of NCL can exist within a particular breed, as appears to be the case among Dachshunds.

Some progress has been made toward the above-stated goal. A mutation in CLN8 is responsible for NCL in English Setters (Katz et al 2005); a mutation in CLN5 is responsible for NCL in Border Collies (Melville et al 2005); and a mutation in CTSD is responsible for NCL in American Bulldogs (Awano et al, 2006). In addition, we recently discovered the mutation for a form of NCL in Longhaired Dachshunds (Awano et al., submitted for publication, 2006). The clinical onset of this Dachshund NCL is much earlier than the Dachshund NCL described in 1980 by Vandevelde and Fatzer, and the ultrastructural appearance of the storage bodies is different, indicating that the Dachshund NCL we studied is a distinct disease. We will publicize the identity of the mutant Dachshund gene as soon as a report of this discovery is accepted for publication in the scientific literature. DNA tests to identify affected, non-symptomatic carriers, and normal dogs are available for these breeds (see below). We are interested in samples from possible affected dogs in the other breeds listed below, or dogs of any breed suspected to have NCL. Please contact us if you suspect you may have an affected dog.