Magnetic resonance imaging of GM2-gangliosidosis in a golden retriever.

G M2-gangliosidoses are a rare group of lysosomal storage diseases caused by excessive accumulation of GM2-ganglioside (GM2) in neurons. They are manifested by progressive neurological disorders involving motor and psychointellectual dysfunctions and visual defects (1). There are 3 main forms of GM2-gangliosidosis: B variant (Tay-Sachs disease), resulting from deficient activity of lysosomal b-hexosaminidase (Hex) A, but normal Hex B; variant 0 (Sandhoff disease) with deficient activities of both Hex A and Hex B; and AB variant, resulting from the GM2-activator protein deficiency instead of normal Hex A and Hex B. Briefly, the deficiency of either Hex A activity or GM2-activator protein results in the accumulation of GM2 and the onset of similar neurologic deterioration. In domestic animals, naturally occurring GM2gangliosidosis has not been investigated to the point of determining a definitive diagnosis because of difficulties with the differential diagnosis based on clinical symptoms and the biochemical diagnosis with specimens from living individuals (2). Thus, until now, the disease has been reported in only 3 canine breeds (3–6), 3 feline breeds (7–9), Yorkshire pigs (10), and Muntjak deer (11). In this report, findings on magnetic resonance imaging (MRI) of a golden retriever with Sandhoff disease are described, previously identified as the 1st canine case with deficiencies of both Hex A and Hex B (6). It also describes clinical and clinicopathologic features of the dog, which were not reported in the initial paper. A 15-month-old, neutered male, golden retriever was referred to the Veterinary Medical Center at the University of Tokyo for evaluation of progressive neurologic abnormalities, including depression, dementia, ataxia, and blindness, which were f irst observed at 11 mo of age. Upon admission, the dog had fallen into a stupor. On physical examination, bilaterally, the pupils were miotic and pupillary light reflexes were absent. The dog did not respond to auditory stimuli. Palpebral reflexes and thoracic and pelvic limb reflexes were weak; however, flexor reflexes seemed normal. All data from a complete blood cell count and serum chemical analysis were within normal ranges. Since serious abnormalities in the central nervous system were suspected, the dog was submitted for an MRI examination on a 0.3 Tesla unit (AIRIS; Hitachi, Tokyo, Japan) without sedation. The nucleus caudatus displayed bilateral T2 hyperintensity and T1 hypointensity (Figure 1A). This lesion was not enhanced by administration of gadolinium-diethylenetriamine penta-acetic acid (DTPA), IV. In addition, mild atrophy of the cerebral cortex was observed, especially in the temporal lobe (Figure 1B). No obvious abnormality was detected in other regions. Analyses of cerebrospinal fluid (CSF) revealed a normal number of leukocytes (, 2/mL), normal glucose (4.5 mmol/L; reference range, 1.9 to 7.8 mmol/L), and total protein concentrations (290 mg/L; reference range, 100 to 400 mg/L). The immunoglobulin-G titer against canine distemper virus was below the detection limit (, 1:3). Glucocorticoids and supportive therapy were not beneficial, and the dog died 1 wk after being admitted. A necropsy was not permitted by the owner. Consequently, tentative diagnosis was established by demonstrating the deficient activities of Hex A and Hex B in peripheral leukocytes, and by determining the level of GM2 in the CSF (2,6). Clinical symptoms of human cases of Sandhoff disease have been reported to be spasticity, dystonia, rigidity, choreiform movements, and blindness (1,12), most of which were observed in the present case. On the other hand, although tonic-clonic or myoclonic seizures are frequently observed in human cases (1), there was no history of seizures in this case. This is the first MRI report of canine GM2-gangliosidosis. While there have been few MRI reports in cases of human GM2-gangliosidoses, abnormal signal intensities in the thalamus and basal ganglion, and cerebral atrophy seem to be the most common findings (12,13). In the early stages of the disease, the thalamus and basal ganglion are reported to exhibit focal T2 hyperintensity and T1 hypointensity, which presumably represent loss of axon and myelin, gliosis, and intralysosomal storage (12). In the later stages, these regions were found to change to hypointense on T2-weighted images due to local calcification (13). On the other hand, an MRI study on feline cases of Sandhoff disease demonstrated the broad hyperintensity of white matter on T2-weighted images (14). The MRI changes observed in this case may be specific to the disease in dogs. An MRI abnormality specific to Departments of Veterinary Clinical Pathobiology (Matsuki, Ono); Veterinary Internal Medicine (Kusuda, Tsujimoto), Graduate School of Agriculture and Life Sciences, the University of Tokyo, Tokyo 113-8657, Japan; Laboratory of Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan (Yamato, Maede).