S-Adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism (CROSBI ID 105157)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Barić, Ivo ; Fumić, Ksenija ; Glen, Byron ; Ćuk, Mario ; Schulze, Andreas ; Finkelstein, James D. ; James, Jill S. ; Mejaški-Bošnjak, Vlatka ; Pažanin, Leo ; Pogribny, Igor P. ; Radoš, Marko ; Sarnavka, Vladimir ; Šćukanec-Špoljar, Mira ; Allen, Robert H. ; Stabler, Sally ; Uzelac, Lidija ; Vugrek, Oliver ; Wagner, Conrad ; Zeisel, Steven ; Mudd, Harvey S.
engleski
S-Adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism
We report studies of a Croatian boy, a proven case of human S-adenosylhomocysteine (AdoHcy) hydrolase deficiency. Psychomotor development was slow until his fifth month ; thereafter, virtually absent until treatment was started. He had marked hypotonia with elevated serum creatine kinase and transaminases, prolonged prothrombin time and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures ; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. Brain MRI at 12.7 months revealed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 μM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant to 14.5–15.9 μM. In plasma, S-adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was ≈3% of control in liver and was 5–10% of the control values in red blood cells and cultured fibroblasts. We found no evidence of a soluble inhibitor of the enzyme in extracts of the patient's cultured fibroblasts. Additional pretreatment abnormalities in plasma included low concentrations of phosphatidylcholine and choline, with elevations of guanidinoacetate, betaine, dimethylglycine, and cystathionine. Leukocyte DNA was hypermethylated. Gene analysis revealed two mutations in exon 4: a maternally derived stop codon, and a paternally derived missense mutation. We discuss reasons for biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency.
Hypermethioninemia ; S-adenosylhomocysteine ; AdoHcy ; homocysteine ; gene mutations
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o izdanju
101 (12)
2004.
4234-4239
objavljeno
0027-8424
10.1073/pnas.0400658101
Povezanost rada
Biologija, Temeljne medicinske znanosti, Kliničke medicinske znanosti