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Sandhoff Disease (sandhoff + disease)
Selected AbstractsCardiac involvement in infantile Sandhoff diseaseJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1 2002P Venugopalan Abstract: An 18-month-old boy with enzyme assay-confirmed infantile Sandhoff disease (MIM 268800) is reported. Besides the classical neurological features, this patient exhibited severe mitral regurgitation secondary to mitral valve prolapse and mild aortic regurgitation from aortic valve prolapse. He also had asymmetric hypertrophy of the interventricular septum without left ventricular outflow tract obstruction. [source] Reduced rates of axonal and dendritic growth in embryonic hippocampal neurones cultured from a mouse model of Sandhoff diseaseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 4 2003D. Pelled Sandhoff disease is a lysosomal storage disease in which ganglioside GM2 accumulates because of a defective ,-subunit of ,-hexosaminidase. This disease is characterized by neurological manifestations, although the pathogenic mechanisms leading from GM2 accumulation to neuropathology are largely unknown. We now examine the viability, development and rates of neurite growth of embryonic hippocampal neurones cultured from a mouse model of Sandhoff disease, the Hexb,/, mouse. GM2 was detected by metabolic labelling at low levels in wild type (Hexb+/+) neurones, and increased by approximately three-fold in Hexb,/, neurones. Hexb,/, hippocampal neurones were as viable as their wild type counterparts and, moreover, their developmental programme was unaltered because the formation of axons and of the minor processes which eventually become dendrites was similar in Hexb,/, and Hexb+/+ neurones. In contrast, once formed, a striking difference in the rate of axonal and minor process growth was observed, with changes becoming apparent after 3 days in culture and highly significant after 5 days in culture. Analysis of various parameters of axonal growth suggested that a key reason for the decreased rate of axonal growth was because of a decrease in the formation of collateral axonal branches, the major mechanism by which hippocampal axons elongate in culture. Thus, although the developmental programme with respect to axon and minor process formation and the viability of hippocampal neurones are unaltered, a significant decrease occurs in the rate of axonal and minor process growth in Hexb,/, neurones. These results appear to be in contrast to dorsal root ganglion neurones cultured from 1-month-old Sandhoff mice, in which cell survival is impaired but normal outgrowth of neurones occurs. The possible reasons for these differences are discussed. [source] Western blotting analysis of the ,-hexosaminidase ,- and ,-subunits in cultured fibroblasts from cases of various forms of GM2 gangliosidosisACTA NEUROLOGICA SCANDINAVICA, Issue 6 2002K. Utsumi Objectives, The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. We examined the , - and , -subunits of , -hexosaminidases by a non-radioisotopes detecting system to evaluate whether it was a useful method for understanding of the pathophysiologies of GM2 gangliosidoses. Materials and methods, We investigated the , - and , -subunits of , -hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system. Results, In a patient with infantile Tay-Sachs disease [HEXA genotype, Int5-SA(g,1,t)/Int5-SA(g,1,t)], the mature , -subunit was undetectable. In a patient with infantile Sandhoff disease (HEXB genotype, C534Y/C534Y), the mature , -subunit was deficient. However, a small amount of the mature , -subunit was detected in a patient with adult Sandhoff disease (HEXB genotype, R505Q(+I207V)/R505Q(+I207V)), which may have resulted in the residual enzyme activity and mild clinical course. Normal amounts of , - and , -subunits were detected in a patient with GM2 activator deficiency. Conclusion, This method is easy and sensitive for detecting target proteins, and is useful for clarification of the pathophysiologies of GM2 gangliosidoses. [source] Defective calcium homeostasis in the cerebellum in a mouse model of Niemann,Pick A diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Luba Ginzburg Abstract We recently demonstrated that calcium homeostasis is altered in mouse models of two sphingolipid storage diseases, Gaucher and Sandhoff diseases, owing to modulation of the activities of a calcium-release channel (the ryanodine receptor) and of the sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA) respectively, by the accumulating sphingolipids. We now demonstrate that calcium homeostasis is also altered in a mouse model of Niemann,Pick A disease, the acid sphingomyelinase (A-SMase)-deficient mouse (ASM,/,), with reduced rates of calcium uptake via SERCA in the cerebellum of 6,7-month-old mice. However, the mechanism responsible for defective calcium homeostasis is completely different from that observed in the other two disease models. Thus, levels of SERCA expression are significantly reduced in the ASM,/, cerebellum by 6,7 months of age, immediately before death of the mice, as are levels of the inositol 1,4,5-triphosphate receptor (IP3R), the major calcium-release channel in the cerebellum. Systematic analyses of the time course of loss of SERCA and IP3R expression revealed that loss of the IP3R preceeded that of SERCA, with essentially no IP3R remaining by 4 months of age, whereas SERCA was still present even after 6 months. Expression of zebrin II (aldolase C), a protein found in about half of the Purkinje cells in the adult mouse cerebellum, was essentially unchanged during development. We discuss possible pathological mechanisms related to calcium dysfunction that may cause Purkinje cell degeneration, and as a result, the onset of neuropathology in Niemann,Pick A disease. [source] | ||||||||||