engleski

Muscle disease in S-adenosylhomocysteine hydrolase deficiency:dystrophy as a consequence of dysmethylation?

Background: S-adenosylhomocysteine hydrolase (SAHH)deficiency is an autosomal recessive methionine cycle disorder. Pathogenesis seems to be complex and inhibit ion of methyl t ransferases due to decreased Sadenosylmethionine/ S-adenosylhomocysteine (AdoMet/AdoHcy) ratio probably contributes to it. Biochemical hallmarks of the disease are elevated AdoHcy, AdoMet and hypermethioninemia. Clinical presentation is variable, but muscle disease with high CK is a constant feature. Methods:We performed pathological studies and muscle MRI to get insight into muscular pathology, and established myoblast cell cultures to test the effect of altered methylation index on muscle in SAHH deficient patients. Results: Muscle biopsy demonstrated destructive myopathy with myelin figures and immunohistochemistry revealed normal expression of muscle structural proteins.Muscle MRI showed degeneration predominantly affecting lower leg muscles and progression correlated with age. Muscle spectroscopy showed increased lipid and water peaks consistent with fatty degeneration and edema.Results on myoblast culture showed different methylation index and structural differences between SAHH deficient and control cell lines under various concentrations of AdoMet and AdoHcy. Conclusion: The pattern of affected muscles and progression with age indicate a contraction-induced injury as seen in dystrophinopathies. Altered methylation seems to be a contributing factor to the muscle pathology. Better understanding of pathogenesis could lead to a more tailored treatment.

Muscle disease; S-adenosylhomocysteine hydrolase deficiency

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