Congenital spongiform leukodystrophy in 2 female littermate German shepherd puppies.

Two 9-week-old female littermate German Shepherd puppies showed severe high-frequency low-amplitude trembling that worsened with movement. The white matter (WM) of the central nervous system (CNS) showed bilateral diffuse severe spongiosis in the cerebellum, brainstem, spinal cord, and the neuropil of the oculomotor and red nuclei. The cortical corona radiata was less severely affected. Rare necrotic or apoptotic glia-like cells also were identified in the WM. Luxol fast blue staining disclosed severe diffuse myelin loss in the entire CNS; peripheral nerves were spared. Glial fibrillary acidic protein immunohistochemistry showed diffuse astrogliosis and astrocytosis in the WM. Genetic analyses of the littermates excluded the aspartoacylase (ASPA) gene as a candidate for this condition in dogs. In conclusion, this description of a rare congenital spongiform leukodystrophy in the German Shepherd breed, closely resembling to Canavan disease in humans, is likely caused by a genetic alteration unrelated to the ASPA gene.

Novel genetic variant associated with globoid cell leukodystrophy in a family of mixed breed dogs.

BACKGROUND: Globoid cell leukodystrophy (GCL) is a fatal autosomal recessive disease caused by variants in the galactosylceramidase (GALC) gene. Two dog breed-specific variants are reported. OBJECTIVES: Characterize the putatively causative GALC variant for GCL in a family of dogs and determine population allele frequency. ANIMALS: Four related mixed-breed puppies with signs of neurologic disease were evaluated. Subsequently, 33 related dogs were tested for genetic markers for parentage and the identified GALC variant. Additional GALC genotyping was performed on 278 banked samples from various breeds. METHODS: The 4 affected puppies had neurological exams and necropsies. DNA was isolated from blood samples. Variants in GALC were identified via Sanger sequencing. Parentage testing was performed using short tandem repeat markers. Prevalence of the GALC variant of interest was investigated in other breeds. RESULTS: GCL was confirmed histopathologically. A novel missense variant in GALC (NC_006590.4:g.58893972G>A) was homozygous in all affected animals (n = 4). A recessive mode of inheritance was confirmed by parentage testing as was variant linkage with the phenotype (LOD = 3.36). Among the related dogs (n = 33), 3 dogs were homozygous and 7 heterozygous. The variant allele was not detected in screening 278 dogs from 5 breeds. The novel variant is either unique to this family or has an extremely low allele frequency in the general population. CONCLUSIONS AND CLINICAL IMPORTANCE: A novel GALC variant was identified that likely explains GCL in this cohort. The identification of multiple causal variants for GCL in dogs is consistent with findings in humans.

Behavioral Changes in Dogs With Idiopathic Epilepsy Compared to Other Medical Populations.

Anxiety related behaviors have been reported in humans diagnosed with idiopathic epilepsy (IE) and such traits may be altered depending on seizure phase. The purpose of this study was to determine the presence and severity of anxiety related behaviors in dogs with IE compared to other medical populations, and to determine if behavioral changes were associated with seizure control. In this retrospective cross-sectional study, the owners of 102 dogs presenting for wellness examination (37), epilepsy (38), and intervertebral disc disease (27) were surveyed utilizing a questionnaire developed based on the shortened Canine Behavioral Assessment and Research Questionnaire (mini-CBARQ), previously validated for its ability to analyze canine behavior. Veterinarians of participating dogs completed a questionnaire to verify diagnoses. Dogs with IE and IVDD had a higher likelihood of being fearful/anxious when approached by an unfamiliar dog compared to the wellness group. Dogs with IE receiving polytherapy had decreased excitement before a walk (P = 0.0007) or car trip (P = 0.027), increased fear/anxiety when groomed (P = 0.0197), and increased shaking, shivering, or trembling when left alone (P = 0.0004) compared to dogs receiving monotherapy. Polytherapy dogs had increased agitation when their owner/others showed affection toward other people/dogs during preictal (Pperson = 0.005, Panimal = 0.0083), postictal (Pperson = 0.001, Panimal = 0.0068), and interictal (Pperson = 0.0083, Panimal = 0.02) period compared to monotherapy dogs. Seizure frequency and severity was not correlated with anxiety related behavior in dogs with IE. While seizure phase was associated with behavior changes in 38% (14/37) of our epileptic population, one specific seizure phase was not more likely to produce behavior changes than another. Behavioral changes noted in dogs with IE raises further questions about how this disease affects QoL. Research was presented in abstract form at the ACVIM Forum, Denver, CO, USA, June 2016.

Comparison of Serum Trace Nutrient Concentrations in Epileptics Compared to Healthy Dogs.

Idiopathic epilepsy (IE) is a common cause of seizures in dogs. There are several investigations regarding serum concentrations of trace nutrients, including copper, selenium, zinc, manganese, and iron in human epileptics and animal models. However, research of this nature in dogs with epilepsy is lacking. The purpose of this prospective study was to compare serum concentrations of several trace nutrients in healthy dogs to dogs with idiopathic epilepsy. Healthy client-owned dogs (n = 50) and dogs with IE (n = 92) were enrolled and blood samples were collected for trace nutrient analysis. Epileptics were subdivided into three groups: controlled: n = 27, uncontrolled: n = 42, and untreated: n = 23. Serum was evaluated for concentrations of copper, selenium, zinc, cobalt, manganese, molybdenum, and iron using inductively coupled plasma mass spectroscopy. Uncontrolled epileptics had significantly higher manganese concentrations compared to normal dogs (p = 0.007). Untreated epileptics had higher iron levels than the other three groups (p = 0.04). Significantly higher levels of copper (p < 0.0001) were found in controlled and uncontrolled epileptics compared to normal or untreated dogs. Significantly higher levels of molybdenum (p = 0.01) were found in controlled epileptics compared to normal or untreated epileptics. Uncontrolled and controlled epileptics had significantly higher levels of selenium (p = 0.0003) vs. normal dogs, and uncontrolled epileptics had higher levels of zinc (p = 0.0002) than normal and untreated dogs. The significant difference in serum concentrations of several trace nutrients (manganese, selenium, and zinc) may suggest a role for these nutrients in the pathophysiology and/or treatment of epilepsy. Additionally, these results suggest that anti-convulsant therapy may affect copper and molybdenum metabolism.