title: S-adenosylhomocysteine hydrolase deficiency in a 26-year-old man.
abstract: This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects.
authors.affiliation: Departments of Pediatrics and Medical Genetics, Oregon Health & Science University, 8510 S.W. White Pine Lane, Portland, OR 97225, USA. Buistnrm@aol.com
authors.forename: N R M
authors.initials: NR
authors.lastname: Buist
authors.forename: B
authors.initials: B
authors.lastname: Glenn
authors.forename: O
authors.initials: O
authors.lastname: Vugrek
authors.forename: C
authors.initials: C
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Stabler
authors.forename: R H
authors.initials: RH
authors.lastname: Allen
authors.forename: I
authors.initials: I
authors.lastname: Pogribny
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: S H
authors.initials: SH
authors.lastname: Zeisel
authors.forename: I
authors.initials: I
authors.lastname: Barić
authors.forename: S H
authors.initials: SH
authors.lastname: Mudd
mesh_terms: D043383:Adenosylhomocysteinase / Q000172:deficiency*; D000328:Adult; D002794:Choline / Q000378:metabolism; D019175:DNA Methylation; D004912:Erythrocytes / Q000378:metabolism; D005192:Family Health; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000473:pathology; D009135:Muscular Diseases / Q000175:diagnosis; D020125:Mutation, Missense; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood
chemical_list: D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D043383:Adenosylhomocysteinase; D002794:Choline