GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido,Japan

A male Japanese domestic cat with retarded growth in Hokkaido, Japan, showed progressive motor dysfunction, such as ataxia starting at 3 months of age and tremors, visual disorder and seizure after 4 months of age. Finally, the cat died of neurological deterioration at 9 months of age. Approximately half of the peripheral blood lymphocytes had multiple abnormal vacuoles. Magnetic resonance imaging showed bisymmetrical hyperintensity in the white matter of the parietal and occipital lobes in the forebrain on T2-weighted and fluid-attenuated inversion recovery images, and mild encephalatrophy of the olfactory bulbs and temporal lobes. The activity of lysosomal acid β-galactosidase in leukocytes was negligible, resulting in the biochemical diagnosis of GM1 gangliosidosis. Histologically, swollen neurons characterized by accumulation of pale, slightly granular cytoplasmic materials were observed throughout the central nervous system. Dysmyelination or demyelination and gemistocytic astrocytosis were observed in the white matter. Ultrastructually, membranous cytoplasmic bodies were detected in the lysosomes of neurons. However, genetic analysis did not identify the c.1448G>C mutation, which is the single known mutation of feline GM1 gangliosidosis, suggesting that the cat was affected with a new variant of the feline disease.     

Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan: possible spread of the mutant allele in the Japanese domestic cat population

GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disease caused by simultaneous deficiencies of acid beta-hexosaminidase (Hex) A and Hex B due to an abnormality of beta-subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. In the present study, a retrospective diagnosis was performed in 2 previous suspected cases of feline Sandhoff-like disease using a DNA test to detect the causative mutation identified previously in 4 cats in 2 other families of Japanese domestic cats. Enzymic analysis was also performed using stored leukocytes and plasma collected from the subject families in order to investigate the usefulness of enzymic diagnosis and genotyping of carriers. The DNA test suggested that the 2 cases were homozygous recessive for the mutation. Consequently, 6 cats homozygous for the same mutation have been found in 4 separate locations of Japan, suggesting that this mutant allele may be spread widely in the Japanese domestic cat populations. In enzymic analysis, Hex A and Hex B activities in leukocytes and plasma measured using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide as a substrate were negligible in affected cats, compared with those in normal and carrier cats. However, there was a wide overlap in enzyme activity between normal and carrier cats. Therefore, it was concluded that enzymic analysis is useful for diagnosis of affected cats, but is not acceptable for genotyping of carriers.     

Canine GM2 gangliosidosis: morphological and biochemical analysis

Beta-hexosaminidase activity and the effects of ganglioside storage on neuronal function were examined in a German shorthair pointer (GSHP) with progressive neurodegenerative signs. Morphologic evidence of neuronal storage and massive accumulation of GM2 ganglioside were present. Beta-hexosaminidase activity in plasma, liver, kidney, and brain, assayed with use of unsulfated fluorogenic substrates, was normal. There was no pathologic accumulation or aberrant localization of phosphorylated neurofilaments in neurons. Activity of cortical neurotransmitter synthesizing enzymes, choline acetyltransferase, and glutamate decarboxylase was unaffected. Ligand binding to carrier sites for choline high affinity uptake identified with [3H]hemicholinium-3 was increased, whereas post-synaptic binding to muscarinic cholinergic ([3H]QNB) and gamma-aminobutyric acid receptors ([3H]muscimol) was reduced.     

Pathology of GM2 gangliosidosis in Jacob sheep

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.     

Morphological analysis of corneal opacity in Shiba dog with GM1 gangliosidosis

GM1 gangliosidosis is one of the inherited metabolic lysosomal storage disorders characterized by neurological symptoms caused by beta-galactosidase deficiency and consequent accumulation of GM1 ganglioside in neuronal cells. Shiba dogs affected with GM1 gangliosidosis have been found to suffer from corneal opacity. In our morphological analysis, keratocyte enlargement was induced by abnormal intracellular accumulation of neutral carbohydrates, resulting in the loss of normal arrangement of collagen fibrils in the opaque cornea was found to be associated with the disorder. We therefore conclude that corneal opacity in this Shiba dog with GM1 gangliosidosis may be caused by neutral carbohydrate accumulation in lysosomes, swelling and dysfunction of keratocytes, and subsequent irregular arrangement of collagen fibrils in the corneal proper substance.     

Clinical use of echocardiography in the domestic cat

Echocardiograms were obtained from unanesthetized cats positioned in left lateral recumbency. Information regarding chamber wall thickness, lumen dimensions, valve motion, and indices of contractility was obtained. In three cases, echocardiographic manifestations typical of cardiac dilatation, cardiac hypertrophy, and pericardial effusion were recorded. Unlike thoracic radiographs, which portray pulmonary features as well as a cardiac silhouette, the echocardiogram provided an opportunity to measure each component comprising the cardiac silhouette--namely, the pericardial sac, cardiac musculature, and the cardiac chambers.     

GM2-gangliosidosis variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats

A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism developed neurological disorders, including ataxia, decreased postural responses and generalised body and head tremors, at between two and five months of age. Leucocytosis due to lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at 10 months of age. Histopathologically, neurons throughout the central nervous system were distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these distended neurons. The compound which accumulated in the brain was identified as G(M2)-ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were less than half the normal value. The Sandhoff-like disease observed in this family of Japanese domestic cats is the first occurrence reported in Japan.     

Hepatozoonosis in two species of Japanese wild cat

Hepatozoon sp. infections were detected in two species of Japanese wild cat, Iriomote wild cat (Felis iriomotensis) and Tsushima leopard cat (Felis bengalensis euptilura), between April 1993 and October 2005. The prevalence was 56.7% (17/30) and 14.3% (6/42), respectively. The most affected organ was the heart; all infected animals had organisms in their hearts. The parasitizing form was schizont and various developmental stages were observed. The size of schizont and merozoite was 22.3 +/- 3.1 x 15.3 +/- 2.2 mum and 6.1 +/- 0.6 x 2.3 +/- 0.2 mum, respectively. Few inflammatory reactions against the parasites were observed. Electron microscopically, organisms were located in parasitophorous vacuoles of unidentified host cells, and mature schizonts consisted of numerous merozoites. This is the first report of hepatozoonosis in Japanese felids.     

The glycosaminoglycan content of the liver in bovine GM1 gangliosidosis.

Chemical analysis of the livers from four calves with GM1 gangliosidosis was negative for significantly elevated levels of glycosaminoglycans. The chemical findings confirmed morphological studies in which hepatic changes were minimal or absent. The findings were compared with the published evidence for the hepatic storage of glycosaminoglycans in human GM1 gangliosidosis.     

Pharmacokinetics of cefotaxime in the domestic cat

Cefotaxime was administered as single IV or IM dose for the purpose of examining its pharmacokinetics in healthy cats. The mean predicted plasma concentration of cefotaxime in 6 cats at 0 time after a single IV dosage of 10 mg/kg of body weight was 88.9 micrograms/ml. The mean plasma concentrations decreased to 10.8 micrograms/ml at 2 hours, 3.7 micrograms/ml at 3 hours, and 0.5 microgram/ml at 6 hours. The half-life was 0.98 +/- 0.25 hour (mean +/- SD), and the total body clearance was determined to be 2.76 +/- 1.25 ml/min/kg. After a single IM injection of 10 mg/kg of body weight, the mean maximum observed plasma concentration was 36.2 micrograms/ml at 0.75 hour. The mean absorption half-life was 0.24 hour. In 2 animals, the bioavailability of an IM injection was 98.2% and 93.0%.     

Accumulation of mercury and selenium in tissues of kittens fed commercial cat food

Six kittens, three males and three females, were fed exclusively for one hundred days a commercially canned red meat tuna found to contain elevated concentrations of Mercury (Hg) and Selenium (Se). A similarly sized control group was fed for the same period a dry commercial cat food comparatively low in the concentration of these elements. At the end of the feeding trial, concentrations of Hg Se were markedly higher in blood, bone, brain, kidney, liver, muscle and spleen of the kittens fed the tuna diet as compared to the corresponding controls. No behavioral abnormalities or pathological lesions were detected in any of the kittens.     

Clinical and clinico-pathologic characteristics of Shiba dogs with a deficiency of lysosomal acid beta-galactosidase: a canine model of human GM1 gangliosidosis

The present study was conducted to determine the clinical and clinico-pathologic characteristics of Shiba dogs with GM1 gangliosidosis, which is due to an autosomal recessively inherited deficiency of lysosomal acid beta-galactosidase activity. Clinical and clinico-pathological features were investigated in 10 homozygous Shiba dogs with GM1 gangliosidosis. The age at onset was 5 to 6 months and the dogs manifested progressive neurologic signs including loss of balance, intermittent lameness, ataxia, dysmetria and intention tremor of the head. The dogs were unable to stand by 10 months of age due to a progression of ataxia and spasticity in all limbs. Corneal clouding, a visual defect, generalized muscle rigospasticity, emotional disorder and a tendency to be lethargic were observed at 9 to 12 months. The dogs became lethargic from 13 months of age. The survival period seemed to be 14 to 15 months. As a clinico-pathologic feature, lymphocytes with abnormally large vacuoles were observed in peripheral blood (30 to 50% of total lymphocytes) through the lifetime of the dogs. The clinical and clinico-pathologic characteristics of this animal model are useful for not only the development and testing of potential methods of therapy, but also the diagnosis of affected homozygous Shiba dogs in veterinary clinics.     

Natural and experimental pox virus infection in the domestic cat

Three naturally occurring cases of cowpox virus infection in the domestic cat are described. Isolate L97 was identified as cowpox virus on the basis of morphology, serology and characteristic cytopathic effect in tissue culture and on the chorioallantoic membrane of embryonated eggs. All three cases showed multiple skin lesions, slight conjunctivitis or purulent ocular discharge but there were no respiratory signs. Two animals recovered, the third was put down as a stray. The disease was reproduced in experimental cats. Isolate L97 was inoculated into two cats intravenously and two cats by skin scarification. All four developed skin lesions at the site or sites of inoculation, and in one cat multiple lesions developed. The two intravenously inoculated animals also developed severe oedema of the neck and brisket around the site of inoculation into the jugular vein, and one cat died. Serological and pathological findings on both the natural and experimental infections are described. Serum neutralising antibody titres in both natural and experimental early convalescent cases were significantly enhanced by the addition of complement.     

Clinical applications and characteristics of apparent diffusion coefficient maps for the brain of two dogs

Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping are functional magnetic resonance imaging techniques for detecting water diffusion. DWI and the ADC map were performed for intracranial lesions in two dogs. In necrotizing leukoencephalitis, cavitated lesions contained a hypointense center with a hyperintense periphery on DWI, and hyperintense signals on the ADC maps. In metastatic sarcoma, masses including a necrotic region were hypointense with DWI, and hyperintense on the ADC map with hyperintense perilesional edema on DWI and ADC map. Since DWI and ADC data reflect the altered water diffusion, they can provide additional information at the molecular level.