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

Autori
Petković Ramadža, Danijela ; Majić, Željka ; Ćuk, Mario ; Prutki M, Brčić L, Zekušić Marija ; Lochmüller, Hanns ; Pažanin, Lidija ; Žarković, K ; Bilić, Karmen ; Sarnavka, Vladimir ; Barišić, Nina ; Fumić, Ksenija ; Barić, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
J Inherit Metab Dis (2015) 38 (Suppl 1):S35–S378 / - , 2015

Skup
SSIEM 2015 Annual Symposium

Mjesto i datum
Lyon, Francuska, 01.09.2015. - 04.09.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Muscle disease; S-adenosylhomocysteine hydrolase deficiency

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA