GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.

G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal ß-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid ß-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population.

Sepsis and disseminated intravascular coagulation in an eastern spiny softshell turtle (Apalone spinifera spinifera) with acute mycobacteriosis.

An adult, captive eastern spiny softshell turtle (Apalone spinifera spinifera) was examined for a 4-day history of lethargy and plastron discoloration. The turtle was obtunded and had pale mucous membranes, hemorrhagic nasal discharge, and petechiae on all limbs. The turtle was euthanized due to its grave condition. Necropsy revealed hemorrhagic coelomic effusion, petechiae on the serosal surfaces of the intestinal tract, and bilaterally hemorrhagic lungs. Histologic examination revealed numerous emboli of bacteria associated with fibrinocellular thrombi throughout the blood vessels of multiple tissues. The bacteria in the thrombi were slender bacilli that stained intensely acid fast. Culture of the coelomic fluid yielded Mycobacterium chelonae. Although mycobacteriosis in reptiles is typically a chronic, granulomatous disease, this case demonstrates that mycobacteriosis should be considered in reptiles presenting with acute, nongranulomatous disease. This case also describes clinically apparent hemorrhage due to disseminated intravascular coagulation, which is rarely described in chelonians.