Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine
The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these...
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| Veröffentlicht in: | The New England journal of medicine 1983-08, Vol.309 (8), p.448-453 |
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| creator | Wilcken, David E. L Wilcken, Bridget Dudman, Nicholas P. B Tyrrell, Pauline A |
| description | The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine β-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P |
| doi_str_mv | 10.1056/NEJM198308253090802 |
| format | Article |
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THE inborn errors of methionine metabolism that result in homocystinuria are of special interest, because, like homozygous familial hyperlipoproteinemia, they provide a model for premature atherogenesis in human beings. Homocystinuria has an incidence of approximately 1 in 60,000 in New South Wales, Australia
1
(although lower incidences have been reported elsewhere
2
), and is usually due to diminished activity of cystathionine β-synthase (EC 4.2.1.22), which condenses homocysteine and serine to form cystathionine (Fig. 1 and
2
). As a consequence, plasma concentrations of homocysteine, cysteine–homocysteine, and methionine are elevated, and the level of cysteine is decreased. In addition to thromboembolism and early atherosclerosis . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJM198308253090802</identifier><identifier>PMID: 6877313</identifier><language>eng</language><publisher>United States: Massachusetts Medical Society</publisher><subject>Amino acids ; Amino Acids - blood ; Amino Acids, Sulfur - blood ; Atherosclerosis ; Betaine ; Betaine - administration & dosage ; Betaine - therapeutic use ; Cystathionine beta-Synthase - deficiency ; Cysteine - blood ; Defects ; Diet ; Enzymes ; Female ; Homocysteine ; Homocysteine - blood ; Homocystinuria ; Homocystinuria - drug therapy ; Humans ; Male ; Metabolism ; Patients ; Pyridoxine ; Pyridoxine - therapeutic use ; Sulfur ; Vitamin B ; Vitamin B 12 - metabolism ; Vitamin B12</subject><ispartof>The New England journal of medicine, 1983-08, Vol.309 (8), p.448-453</ispartof><rights>Copyright Massachusetts Medical Society Aug 25, 1983</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-f43b3412d81187945e35d6d2600198f6d5184a7f7d853feb00cbc9f0039b93483</citedby><cites>FETCH-LOGICAL-c401t-f43b3412d81187945e35d6d2600198f6d5184a7f7d853feb00cbc9f0039b93483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1875427076?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/6877313$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wilcken, David E. L</creatorcontrib><creatorcontrib>Wilcken, Bridget</creatorcontrib><creatorcontrib>Dudman, Nicholas P. B</creatorcontrib><creatorcontrib>Tyrrell, Pauline A</creatorcontrib><title>Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine β-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P<0.001) and an increase in total cysteine levels (P<0.001). Changes in plasma methionlne concentrations were variable. Fasting levels of plasma amino acids became normal in two patients, and in six there was immediate clinical improvement. There were no unwanted effects. We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels. (N Engl J Med 1983; 309: 448–53.)
THE inborn errors of methionine metabolism that result in homocystinuria are of special interest, because, like homozygous familial hyperlipoproteinemia, they provide a model for premature atherogenesis in human beings. Homocystinuria has an incidence of approximately 1 in 60,000 in New South Wales, Australia
1
(although lower incidences have been reported elsewhere
2
), and is usually due to diminished activity of cystathionine β-synthase (EC 4.2.1.22), which condenses homocysteine and serine to form cystathionine (Fig. 1 and
2
). As a consequence, plasma concentrations of homocysteine, cysteine–homocysteine, and methionine are elevated, and the level of cysteine is decreased. In addition to thromboembolism and early atherosclerosis . . .</description><subject>Amino acids</subject><subject>Amino Acids - blood</subject><subject>Amino Acids, Sulfur - blood</subject><subject>Atherosclerosis</subject><subject>Betaine</subject><subject>Betaine - administration & dosage</subject><subject>Betaine - therapeutic use</subject><subject>Cystathionine beta-Synthase - deficiency</subject><subject>Cysteine - blood</subject><subject>Defects</subject><subject>Diet</subject><subject>Enzymes</subject><subject>Female</subject><subject>Homocysteine</subject><subject>Homocysteine - blood</subject><subject>Homocystinuria</subject><subject>Homocystinuria - drug therapy</subject><subject>Humans</subject><subject>Male</subject><subject>Metabolism</subject><subject>Patients</subject><subject>Pyridoxine</subject><subject>Pyridoxine - therapeutic use</subject><subject>Sulfur</subject><subject>Vitamin B</subject><subject>Vitamin B 12 - metabolism</subject><subject>Vitamin B12</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1983</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9UV9LHDEQD0WxV9tPUAqBgi-yOtkku8ljPc5aUSvl-rzsnwnNcbs5k6x4b34IP6GfpDnu8EHEmYcZ-P2ZYYaQrwxOGMji9GZ2ec204qByyUGDgvwDmTDJeSYEFHtkApCrTJSafySfQlhACib0ATkoVFlyxiekvXC9a9ch2mH0tqbPj090_g_pzBhsY6DO0DOMtR2Q2oHGhMw91rHHIW6w2zra1AZ64yL9g2HlhmDvkUZHb9fedu4hKT-TfVMvA37Z1UPy93w2n15kV79__pr-uMpaASxmRvCGC5Z3ijFVaiGRy67o8iItrZUpOsmUqEtTdkpygw1A27TaAHDdaC4UPyRHW9-Vd3cjhlj1NrS4XNYDujFUCqRKWSTi91fEhRv9kHar0mQp8hLKDYtvWa13IXg01crbvvbrikG1eUD1xgOS6tvOe2x67F40u4sn_HiL932oBlz077r9B9TWjC0</recordid><startdate>19830825</startdate><enddate>19830825</enddate><creator>Wilcken, David E. 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L ; Wilcken, Bridget ; Dudman, Nicholas P. B ; Tyrrell, Pauline A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-f43b3412d81187945e35d6d2600198f6d5184a7f7d853feb00cbc9f0039b93483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1983</creationdate><topic>Amino acids</topic><topic>Amino Acids - blood</topic><topic>Amino Acids, Sulfur - blood</topic><topic>Atherosclerosis</topic><topic>Betaine</topic><topic>Betaine - administration & dosage</topic><topic>Betaine - therapeutic use</topic><topic>Cystathionine beta-Synthase - deficiency</topic><topic>Cysteine - blood</topic><topic>Defects</topic><topic>Diet</topic><topic>Enzymes</topic><topic>Female</topic><topic>Homocysteine</topic><topic>Homocysteine - blood</topic><topic>Homocystinuria</topic><topic>Homocystinuria - drug therapy</topic><topic>Humans</topic><topic>Male</topic><topic>Metabolism</topic><topic>Patients</topic><topic>Pyridoxine</topic><topic>Pyridoxine - therapeutic use</topic><topic>Sulfur</topic><topic>Vitamin B</topic><topic>Vitamin B 12 - metabolism</topic><topic>Vitamin B12</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wilcken, David E. L</creatorcontrib><creatorcontrib>Wilcken, Bridget</creatorcontrib><creatorcontrib>Dudman, Nicholas P. 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L</au><au>Wilcken, Bridget</au><au>Dudman, Nicholas P. B</au><au>Tyrrell, Pauline A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>1983-08-25</date><risdate>1983</risdate><volume>309</volume><issue>8</issue><spage>448</spage><epage>453</epage><pages>448-453</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><abstract>The treatment of homocystinuria that is not responsive to pyridoxine is not usually biochemically or clinically successful, and vascular, ocular, and skeletal complications commonly supervene. Persistent marked homocysteinemia appears to be the most important biochemical disturbance leading to these complications. Ten patients with cystathionine β-synthase deficiency that was not responsive to pyridoxine and one patient with homocystinuria due to a defect in cobalamin metabolism were treated with 6 g daily of betaine added to conventional therapy, to improve homocysteine remethylation. All patients had a substantial decrease in plasma total homocysteine levels (P<0.001) and an increase in total cysteine levels (P<0.001). Changes in plasma methionlne concentrations were variable. Fasting levels of plasma amino acids became normal in two patients, and in six there was immediate clinical improvement. There were no unwanted effects. We conclude that treatment of homocystinuria that is not responsive to pyridoxine and of disorders of homocysteine remethylation should include betaine in adequate doses to ensure maximum lowering of elevated plasma homocysteine levels. (N Engl J Med 1983; 309: 448–53.)
THE inborn errors of methionine metabolism that result in homocystinuria are of special interest, because, like homozygous familial hyperlipoproteinemia, they provide a model for premature atherogenesis in human beings. Homocystinuria has an incidence of approximately 1 in 60,000 in New South Wales, Australia
1
(although lower incidences have been reported elsewhere
2
), and is usually due to diminished activity of cystathionine β-synthase (EC 4.2.1.22), which condenses homocysteine and serine to form cystathionine (Fig. 1 and
2
). As a consequence, plasma concentrations of homocysteine, cysteine–homocysteine, and methionine are elevated, and the level of cysteine is decreased. In addition to thromboembolism and early atherosclerosis . . .</abstract><cop>United States</cop><pub>Massachusetts Medical Society</pub><pmid>6877313</pmid><doi>10.1056/NEJM198308253090802</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-4793 |
| ispartof | The New England journal of medicine, 1983-08, Vol.309 (8), p.448-453 |
| issn | 0028-4793 1533-4406 |
| language | eng |
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| source | MEDLINE; ProQuest Central UK/Ireland |
| subjects | Amino acids Amino Acids - blood Amino Acids, Sulfur - blood Atherosclerosis Betaine Betaine - administration & dosage Betaine - therapeutic use Cystathionine beta-Synthase - deficiency Cysteine - blood Defects Diet Enzymes Female Homocysteine Homocysteine - blood Homocystinuria Homocystinuria - drug therapy Humans Male Metabolism Patients Pyridoxine Pyridoxine - therapeutic use Sulfur Vitamin B Vitamin B 12 - metabolism Vitamin B12 |
| title | Homocystinuria — The Effects of Betaine in the Treatment of Patients Not Responsive to Pyridoxine |
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