title: Spontaneous perforation of the small intestine, a novel manifestation of classical homocystinuria in an adult with new cystathionine beta-synthetase gene mutations.
abstract: The clinical picture of classical homocystinuria is diverse. This is the first report of an adult homocystinuric patient with non-traumatic spontaneous small bowel perforation. A 47-year old man presented with abdominal rebound tenderness, hypotension and tachycardia, anemia, and elevated markers of inflammation. Other routine laboratory tests were normal. Abdominal x-ray showed no free air. An emergency laparotomy revealed jejunal perforation in the left upper quadrant. Histologic specimen showed full-thickness nonspecific inflammation of the intestinal wall with granulocytic infiltration, hemorrhage and necrosis. Tuberculosis, actinomycosis and typhus were histologically and clinically excluded. After excluding all known possible causes of perforation, we presumed a causative relationship between homocystinuria and small bowel perforation. It could be hypothesized that connective tissue weakness in homocystinuria is a result of homocysteine interference with recombinant human fibrillin-1 fragments or cross-linking of collagen through permanent degradation of disulfide bridges and lysine amino acid residues in proteins. DNA analysis showed three detectable mutations in the cystathionine beta-synthetase gene, 1278T:c.833T>C, and two new mutations, V372G:c.1133T > G, and D520G:c.1558A > G in the aternatively spliced exon 15.
authors.affiliation: University of Zagreb, Zagreb University Hospital Center, Department of Internal Medicine, Division for Metabolic Diseases, Zagreb, Croatia. dmuacevi@mef.hr
authors.forename: Diana
authors.initials: D
authors.lastname: Muacević-Katanec
authors.forename: Tihomir
authors.initials: T
authors.lastname: Kekez
authors.forename: Ksenija
authors.initials: K
authors.lastname: Fumić
authors.forename: Ivo
authors.initials: I
authors.lastname: Barić
authors.forename: Marijan
authors.initials: M
authors.lastname: Merkler
authors.forename: Jasminka
authors.initials: J
authors.lastname: Jakić-Razumović
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Krznarić
authors.forename: Renata
authors.initials: R
authors.lastname: Zadro
authors.forename: Davor
authors.initials: D
authors.lastname: Katanec
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Reiner
mesh_terms: D003541:Cystathionine beta-Synthase / Q000235:genetics*; D006712:Homocystinuria / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007416:Intestinal Perforation / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009336:Necrosis
chemical_list: D003541:Cystathionine beta-Synthase