g(m1)-ganglioside and Mucopolysaccharidosis-I

Topics: G(M1) Ganglioside; G(M2) Ganglioside; G(M3) Ganglioside; Gangliosidoses; Genetic Carrier Screening; Genetic Counseling; Glycoside Hydrolases; Humans; Leukodystrophy, Metachromatic; Lipidoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Mucopolysaccharidosis IV; Mucopolysaccharidosis VI; Phenotype; Polymorphism, Genetic

Mucopolysaccharidosis I (MPS I) is a congenital disorder caused by the deficiency of α-l-iduronidase (IDUA), with the accumulation of glycosaminoglycans (GAGs) in the CNS. Although GAG toxicity is not fully understood, previous works suggest a GAG-induced alteration in neuronal membrane composition. This study is aimed to evaluate the levels and distribution of gangliosides and cholesterol in different brain regions (cortex, cerebellum, hippocampus and hypothalamus) in a model using IDUA knockout (KO) mice (C57BL/6). Lipids were extracted with chloroform-methanol and then total gangliosides and cholesterol were determined, followed by ganglioside profile analyses. While no changes in cholesterol content were observed, the results showed a tissue dependent ganglioside alteration in KO mice: a total ganglioside increase in cortex and cerebellum, and a selective presence of GM3, GM2 and GD3 gangliosides in the hippocampus and hypothalamus. To elucidate this, we evaluated gene expression of ganglioside synthesis (GM3, GD3 and GM2/GD2 synthases) and degradation of (Neuraminidase1) enzymes in the cerebellum and hippocampus by RT-sq-PCR. The results obtained with KO mice showed a reduced expression of GD3 and GM2/GD2 synthases and Neuraminidase1 in cerebellum; and a decrease in GM2/GD2 synthase and Neuraminidase1 in the hippocampus. These data suggest that the observed ganglioside changes result from a combined effect of GAGs on ganglioside biosynthesis and degradation.

Topics: Animals; Brain; Cerebellum; Cerebral Cortex; Cholesterol; Disease Models, Animal; G(M1) Ganglioside; Gene Expression; Hippocampus; Hypothalamus; Membrane Lipids; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucopolysaccharidosis I; N-Acetylgalactosaminyltransferases; Neuraminidase; Sialyltransferases

This communication reports the clinical and biochemical results in six patients: four with mucopolysaccharidosis, one with GM1 gangliosidosis (Morquio B) and one with I-cell disease, who were treated by amniotic tissue transplantation. The sole evident clinical result was the diminishing of corneal clouding in three cases. A slight increase of beta-galactosidase activity in one patient's plasma was observed. The time of improvement was about 2 months after the transplantation and was transitory.

Topics: Amnion; Child; Child, Preschool; Female; G(M1) Ganglioside; Gangliosidoses; Humans; Male; Mucolipidoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis VI

Topics: Acetylglucosaminidase; Arylsulfatases; beta-Galactosidase; Brain; Cerebrosides; Child, Preschool; Female; G(M1) Ganglioside; Glucuronidase; Hexosamines; Humans; Lactose Intolerance; Lipid Metabolism; Mucolipidoses; Mucopolysaccharidosis I; Organ Specificity; Sialic Acids; Sphingolipids