A Variant Form of Neuronal Ceroid Lipofuscinosis in American Bulldogs

Abstract

Neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases characterized by accumulations of autofluorescent lipopigments within cells of the nervous system. Nine related American Bulldogs demonstrated dysmetria in all limbs and para-paresis. Nonambulatory tetraparesis was observed only in the later stages of the disease. The clinical signs developed between 1 and 3 years of age and were slowly progressive over several years, which is inconsistent with most reports in other breeds. Results from blood tests for 8 different lysosomal storage diseases on 4 affected and 6 related but unaffected dogs were negative. Four affected dogs were euthanized and histopathologic examinations showed diffuse accumulations of periodic acid-Schiff-positive inclusions in neurons and axonal spheroids along the entire neuraxis and retinae. The most severe lesions were in the brainstem proprioceptive nuclei and spinal cord, consistent with clinical signs. The storage material was autofluorescent and immunohisto-chemically positive for products of lipid peroxidation. Ultrastructural analysis was consistent with NCL. Pedigree analysis supports an autosomal-recessive mode of inheritance. NCL has not been previously reported in the American Bulldog and these findings suggest a variant form of the canine disease.

A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund

“…In the cerebellum, the distribution of storage material was more specific, with accumulation occurring primarily in the granular layer. This differs from other canine forms of NCL where significant accumulation of autofluorescent material occurs in the Purkinje cells [25, 42]. …”

Neuronal ceroid lipofuscinosis: clinical and morphologic findings in nine affected Polish Owczarek Nizinny (PON) dogs

“…Eight of the dogs (nos. [1][2][3][4][5][6][7][8] were examined clinically by one of the authors (KN) at the time of euthanasia.…”

“…Electroretinography (ERG) was performed under general anesthesia in five of the dogs (Table 1), utilizing full-field flash stimulation and alternating current (AC) ERG recordings 13,14 in three dogs (nos. [6][7][8] and direct current (DC) ERG recordings 12 in the other two (nos. 3 and 4).…”

“…Recently, the mutation in orthologous genes for the disease was described in the English Setter, the Border Collie and the American Bulldog. Affected dogs were found to have mutations in the CLN8 , CLN5 and in the CTSD genes, respectively 6–9 . Other CLN‐affected breeds, 10 in which extensive molecular genetic studies have been performed – although specific genetic defects have not yet been reported in the literature – are Tibetan Terriers and Long‐haired Dachshunds (Gary Johnson, personal communication, 2006; http://www.caninegeneticdiseases.net).…”

Neuronal Ceroid Lipofuscinosis in 3 Australian Shepherd Littermates

“…Over the past 12 years, the mutations responsible for many of the human NCLs have been identified 7 . A spectrum of NCLs has also been described in a number of dog breeds since Hagen first described the condition in English Setters in 1953 9–15 . To date, mutations in 4 genes have been associated with NCL in dogs: CLN8 in English Setters, 1 CTSD in American Bulldogs, 16 CLN5 in Border Collie dogs, 17 and tripeptidyl peptidase 1 ( CLN2 ) in Miniature Longhaired Dachshunds 9 .…”