{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:14:51Z","timestamp":1791900891849,"version":"4.3.4"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,3,23]]},"abstract":"<jats:p>\n                    We report studies of a Croatian boy, a proven case of human\n                    <jats:italic>S<\/jats:italic>\n                    -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 \u03bcM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant to 14.5\u201315.9 \u03bcM. In plasma,\n                    <jats:italic>S<\/jats:italic>\n                    -adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was \u22483% of control in liver and was 5\u201310% 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0400658101","type":"journal-article","created":{"date-parts":[[2004,3,23]],"date-time":"2004-03-23T13:22:39Z","timestamp":1080048159000},"page":"4234-4239","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":200,"title":["<i>S<\/i>\n                    -adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism"],"prefix":"10.1073","volume":"101","author":[{"given":"Ivo","family":"Bari\u0107","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenija","family":"Fumi\u0107","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron","family":"Glenn","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"\u0106uk","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulze","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Neuropathology, Radiology, and Pathology, and Clinical Institute of Laboratory Diagnosis, University Hospital Center, Ki\u0161pati\u0107eva 12, 10000 Zagreb, Croatia; Department of Biochemistry, Vanderbilt University and Department of Veterans Affairs Medical Center, Nashville, TN 37232-0146; University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany; Veterans Affairs Medical Center and George Washington University, Washington, DC 20422; Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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