Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon in CLN6.

A neutered male domestic medium-haired cat presented at a veterinary neurology clinic at 20 months of age due to progressive neurological signs that included visual impairment, focal myoclonus, and frequent severe generalized seizures that were refractory to treatment with phenobarbital. Magnetic resonance imaging revealed diffuse global brain atrophy. Due to the severity and frequency of its seizures, the cat was euthanized at 22 months of age. Microscopic examination of the cerebellum, cerebral cortex and brainstem revealed pronounced intracellular accumulations of autofluorescent storage material and inflammation in all 3 brain regions. Ultrastructural examination of the storage material indicated that it consisted almost completely of tightly-packed membrane-like material. The clinical signs and neuropathology strongly suggested that the cat suffered from a form of neuronal ceroid lipofuscinosis (NCL). Whole exome sequence analysis was performed on genomic DNA from the affected cat. Comparison of the sequence data to whole exome sequence data from 39 unaffected cats and whole genome sequence data from an additional 195 unaffected cats revealed a homozygous variant in CLN6 that was unique to the affected cat. This variant was predicted to cause a stop gain in the transcript due to a guanine to adenine transition (ENSFCAT00000025909:c.668G > A; XM_003987007.5:c.668G > A) and was the sole loss of function variant detected. CLN6 variants in other species, including humans, dogs, and sheep, are associated with the CLN6 form of NCL. Based on the affected cat's clinical signs, neuropathology and molecular genetic analysis, we conclude that the cat's disorder resulted from the loss of function of CLN6. This study is only the second to identify the molecular genetic basis of a feline NCL. Other cats exhibiting similar signs can now be screened for the CLN6 variant. This could lead to establishment of a feline model of CLN6 disease that could be used in therapeutic intervention studies.

Metabolic Encephalopathy and Lipid Storage Myopathy Associated with a Presumptive Mitochondrial Fatty Acid Oxidation Defect in a Dog.

A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurological examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful, and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurological signs have been described in humans with this group of diseases, descriptions of advanced imaging, and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis, and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

Successful treatment of encrusted cystitis associated with Staphylococcus pseudintermedius infection in the urinary bladder of a dog.

CASE DESCRIPTION: A 5-year-old female spayed mixed-breed dog was examined because of signs of persistent stranguria following treatment for urethral obstruction. CLINICAL FINDINGS: Radiographic, ultrasonographic, cystoscopic, and histologic findings were consistent with encrusted cystitis. Results of bacteriologic culture of urine and bladder wall biopsy samples indicated growth of Staphylococcus pseudintermedius. Treatment and Outcome-The dog was initially treated via IV administration of fluids, placement of an indwelling urinary catheter, lavage of the bladder with sterile saline (0.9% NaCl) solution, and administration of antimicrobial drugs and bethanechol (to improve voiding of urine from the bladder). Antimicrobial drugs were administered for 3 months, and a commercially available diet for dissolution of urinary calculi was fed. Clinical signs of encrusted cystitis gradually resolved during the 3 months after the initial examination. Results of urinalysis and abdominal ultrasonographic examination performed 4 months after the initial examination indicated resolution of the disease. CLINICAL RELEVANCE: Encrusted cystitis is extremely rare in small animals and has previously only been associated with Corynebacterium spp infection of the urinary bladder. Resolution of encrusted cystitis has previously been achieved via surgical debridement of the bladder and treatment with antimicrobial drugs. The clinical findings and successful resolution of clinical signs in the dog of the present report suggested that urease-positive bacteria other than Corynebacterium spp can cause encrusted cystitis and that feeding of a diet for dissolution of urinary calculi in conjunction with antimicrobial treatment may result in resolution of urinary bladder lesions and clinical signs attributable to the disease without the need for surgical debridement of encrusted plaques.