title: S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy.
abstract: S-Adenosylhomocysteine (AdoHcy) hydrolase deficiency has been proven in a human only once, in a recently described Croatian boy. Here we report the clinical course and biochemical abnormalities of the younger brother of this proband. This younger brother has the same two mutations in the gene encoding AdoHcy hydrolase, and has been monitored since birth. We report, as well, outcomes during therapy for both patients. The information obtained suggests that the disease starts in utero and is characterized primarily by neuromuscular symptomatology (hypotonia, sluggishness, psychomotor delay, absent tendon reflexes, delayed myelination). The laboratory abnormalities are markedly increased creatine kinase and elevated aminotransferases, as well as specific amino acid aberrations that pinpoint the aetiology. The latter include, most importantly, markedly elevated plasma AdoHcy. Plasma S-adenosylmethionine (AdoMet) is also elevated, as is methionine (although the hypermethioninaemia may be absent or nonsignificant in the first weeks of life). The disease seems to be at least to some extent treatable, as shown by improved myelination and psychomotor development during dietary methionine restriction and supplementation with creatine and phosphatidylcholine.
authors.affiliation: Department of Pediatrics, University Hospital Center and School of Medicine, Zagreb, Croatia. ibaric@kbc-zagreb.hr
authors.forename: I
authors.initials: I
authors.lastname: Barić
authors.forename: M
authors.initials: M
authors.lastname: Cuk
authors.forename: K
authors.initials: K
authors.lastname: Fumić
authors.forename: O
authors.initials: O
authors.lastname: Vugrek
authors.forename: R H
authors.initials: RH
authors.lastname: Allen
authors.forename: B
authors.initials: B
authors.lastname: Glenn
authors.forename: M
authors.initials: M
authors.lastname: Maradin
authors.forename: L
authors.initials: L
authors.lastname: Pazanin
authors.forename: I
authors.initials: I
authors.lastname: Pogribny
authors.forename: M
authors.initials: M
authors.lastname: Rados
authors.forename: V
authors.initials: V
authors.lastname: Sarnavka
authors.forename: A
authors.initials: A
authors.lastname: Schulze
authors.forename: S
authors.initials: S
authors.lastname: Stabler
authors.forename: C
authors.initials: C
authors.lastname: Wagner
authors.forename: S H
authors.initials: SH
authors.lastname: Zeisel
authors.forename: S H
authors.initials: SH
authors.lastname: Mudd
mesh_terms: D043383:Adenosylhomocysteinase / Q000172:deficiency* / Q000235:genetics*; D000596:Amino Acids / Q000737:chemistry; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D003402:Creatine Kinase / Q000097:blood; D017523:Croatia; D019175:DNA Methylation; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005192:Family Health; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008715:Methionine / Q000378:metabolism; D009154:Mutation; D009186:Myelin Sheath / Q000737:chemistry; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D008715:Methionine; D000637:Transaminases; D003402:Creatine Kinase; D043383:Adenosylhomocysteinase