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NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome
Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmen...
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| Published in: | Clinica chimica acta 2015-02, Vol.440, p.201-204 |
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| creator | Lam, Ching-Wan Law, Chun-Yiu Leung, Ka-Fei Lai, Chi-Kong Pak-lam Chen, Sammy Chan, Bosco Chan, Kwok-yin Yuen, Yuet-ping Mak, Chloe Miu Yan-wo Chan, Albert |
| description | Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmental delay or autistic features. In severe cases, patients may present with profound neurological deficit including hypotonia, seizures and mental retardation. Using NMR-based urinalysis, this condition can be rapidly diagnosed within 15min.
An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC–MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2.
The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC–MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism. |
| doi_str_mv | 10.1016/j.cca.2014.10.030 |
| format | article |
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An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC–MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2.
The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC–MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism.</description><identifier>ISSN: 0009-8981</identifier><identifier>EISSN: 1873-3492</identifier><identifier>DOI: 10.1016/j.cca.2014.10.030</identifier><identifier>PMID: 25445412</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Abnormalities, Multiple - urine ; Amidohydrolases - deficiency ; Amidohydrolases - genetics ; Amidohydrolases - urine ; beta-Alanine - analogs & derivatives ; beta-Alanine - urine ; Brain Diseases - urine ; Dravet syndrome ; Dual molecular diagnoses ; Epilepsies, Myoclonic - complications ; Epilepsies, Myoclonic - genetics ; Epilepsies, Myoclonic - urine ; Gas Chromatography-Mass Spectrometry - methods ; Homozygote ; Humans ; Infant ; Magnetic Resonance Spectroscopy - methods ; Male ; Movement Disorders - urine ; NAV1.1 Voltage-Gated Sodium Channel - genetics ; NMR spectroscopy ; Purine-Pyrimidine Metabolism, Inborn Errors - urine ; Urea - analogs & derivatives ; Urea - urine ; Urinalysis - methods ; β-Ureidopropionase deficiency</subject><ispartof>Clinica chimica acta, 2015-02, Vol.440, p.201-204</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-22db56520d1423b86a5f8d4d89f6c0aee03b1044b3704fda09a95ae0f65b189c3</citedby><cites>FETCH-LOGICAL-c353t-22db56520d1423b86a5f8d4d89f6c0aee03b1044b3704fda09a95ae0f65b189c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25445412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lam, Ching-Wan</creatorcontrib><creatorcontrib>Law, Chun-Yiu</creatorcontrib><creatorcontrib>Leung, Ka-Fei</creatorcontrib><creatorcontrib>Lai, Chi-Kong</creatorcontrib><creatorcontrib>Pak-lam Chen, Sammy</creatorcontrib><creatorcontrib>Chan, Bosco</creatorcontrib><creatorcontrib>Chan, Kwok-yin</creatorcontrib><creatorcontrib>Yuen, Yuet-ping</creatorcontrib><creatorcontrib>Mak, Chloe Miu</creatorcontrib><creatorcontrib>Yan-wo Chan, Albert</creatorcontrib><title>NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome</title><title>Clinica chimica acta</title><addtitle>Clin Chim Acta</addtitle><description>Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmental delay or autistic features. In severe cases, patients may present with profound neurological deficit including hypotonia, seizures and mental retardation. Using NMR-based urinalysis, this condition can be rapidly diagnosed within 15min.
An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC–MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2.
The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC–MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism.</description><subject>Abnormalities, Multiple - urine</subject><subject>Amidohydrolases - deficiency</subject><subject>Amidohydrolases - genetics</subject><subject>Amidohydrolases - urine</subject><subject>beta-Alanine - analogs & derivatives</subject><subject>beta-Alanine - urine</subject><subject>Brain Diseases - urine</subject><subject>Dravet syndrome</subject><subject>Dual molecular diagnoses</subject><subject>Epilepsies, Myoclonic - complications</subject><subject>Epilepsies, Myoclonic - genetics</subject><subject>Epilepsies, Myoclonic - urine</subject><subject>Gas Chromatography-Mass Spectrometry - methods</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Infant</subject><subject>Magnetic Resonance Spectroscopy - methods</subject><subject>Male</subject><subject>Movement Disorders - urine</subject><subject>NAV1.1 Voltage-Gated Sodium Channel - genetics</subject><subject>NMR spectroscopy</subject><subject>Purine-Pyrimidine Metabolism, Inborn Errors - urine</subject><subject>Urea - analogs & derivatives</subject><subject>Urea - urine</subject><subject>Urinalysis - methods</subject><subject>β-Ureidopropionase deficiency</subject><issn>0009-8981</issn><issn>1873-3492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kE1u2zAQhYkiRe24PUA3BZfZyBmKlCyhq8L5BZwECNo1QZHDhIYsqqTkwNfqQXKm0LXbZVaDN3jvYeYj5CuDOQNWnq_nWqt5DkwkPQcOH8iUVQuecVHnJ2QKAHVW1RWbkNMY10kKKNknMskLIQrB8ilp7-8es0ZFNHQMrlPtLrpIrQ80qN4Zapx66vx-5y19_ZONAZ3xffC9812KUYPWaYed3lHXUUV7NSQ10Bc3PNOLoLY40LjrTPAb_Ew-WtVG_HKcM_Lr6vLn8iZbPVzfLn-sMs0LPmR5bpqiLHIwTOS8qUpV2MoIU9W21KAQgTcMhGj4AoQ1CmpVFwrBlkXDqlrzGTk79KY7f48YB7lxUWPbqg79GCVL5YKLSrBkZQerDj7GgFb2wW1U2EkGcg9ZrmWCLPeQ96sEOWW-HevHZoPmf-If1WT4fjBgenLrMMj4FxEaF1AP0nj3Tv0b73SOSA</recordid><startdate>20150202</startdate><enddate>20150202</enddate><creator>Lam, Ching-Wan</creator><creator>Law, Chun-Yiu</creator><creator>Leung, Ka-Fei</creator><creator>Lai, Chi-Kong</creator><creator>Pak-lam Chen, Sammy</creator><creator>Chan, Bosco</creator><creator>Chan, Kwok-yin</creator><creator>Yuen, Yuet-ping</creator><creator>Mak, Chloe Miu</creator><creator>Yan-wo Chan, Albert</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150202</creationdate><title>NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome</title><author>Lam, Ching-Wan ; Law, Chun-Yiu ; Leung, Ka-Fei ; Lai, Chi-Kong ; Pak-lam Chen, Sammy ; Chan, Bosco ; Chan, Kwok-yin ; Yuen, Yuet-ping ; Mak, Chloe Miu ; Yan-wo Chan, Albert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-22db56520d1423b86a5f8d4d89f6c0aee03b1044b3704fda09a95ae0f65b189c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Abnormalities, Multiple - urine</topic><topic>Amidohydrolases - deficiency</topic><topic>Amidohydrolases - genetics</topic><topic>Amidohydrolases - urine</topic><topic>beta-Alanine - analogs & derivatives</topic><topic>beta-Alanine - urine</topic><topic>Brain Diseases - urine</topic><topic>Dravet syndrome</topic><topic>Dual molecular diagnoses</topic><topic>Epilepsies, Myoclonic - complications</topic><topic>Epilepsies, Myoclonic - genetics</topic><topic>Epilepsies, Myoclonic - urine</topic><topic>Gas Chromatography-Mass Spectrometry - methods</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Infant</topic><topic>Magnetic Resonance Spectroscopy - methods</topic><topic>Male</topic><topic>Movement Disorders - urine</topic><topic>NAV1.1 Voltage-Gated Sodium Channel - genetics</topic><topic>NMR spectroscopy</topic><topic>Purine-Pyrimidine Metabolism, Inborn Errors - urine</topic><topic>Urea - analogs & derivatives</topic><topic>Urea - urine</topic><topic>Urinalysis - methods</topic><topic>β-Ureidopropionase deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lam, Ching-Wan</creatorcontrib><creatorcontrib>Law, Chun-Yiu</creatorcontrib><creatorcontrib>Leung, Ka-Fei</creatorcontrib><creatorcontrib>Lai, Chi-Kong</creatorcontrib><creatorcontrib>Pak-lam Chen, Sammy</creatorcontrib><creatorcontrib>Chan, Bosco</creatorcontrib><creatorcontrib>Chan, Kwok-yin</creatorcontrib><creatorcontrib>Yuen, Yuet-ping</creatorcontrib><creatorcontrib>Mak, Chloe Miu</creatorcontrib><creatorcontrib>Yan-wo Chan, Albert</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinica chimica acta</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lam, Ching-Wan</au><au>Law, Chun-Yiu</au><au>Leung, Ka-Fei</au><au>Lai, Chi-Kong</au><au>Pak-lam Chen, Sammy</au><au>Chan, Bosco</au><au>Chan, Kwok-yin</au><au>Yuen, Yuet-ping</au><au>Mak, Chloe Miu</au><au>Yan-wo Chan, Albert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome</atitle><jtitle>Clinica chimica acta</jtitle><addtitle>Clin Chim Acta</addtitle><date>2015-02-02</date><risdate>2015</risdate><volume>440</volume><spage>201</spage><epage>204</epage><pages>201-204</pages><issn>0009-8981</issn><eissn>1873-3492</eissn><notes>ObjectType-Case Study-2</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-4</notes><notes>content type line 23</notes><notes>ObjectType-Report-1</notes><notes>ObjectType-Article-3</notes><abstract>Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmental delay or autistic features. In severe cases, patients may present with profound neurological deficit including hypotonia, seizures and mental retardation. Using NMR-based urinalysis, this condition can be rapidly diagnosed within 15min.
An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC–MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2.
The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC–MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25445412</pmid><doi>10.1016/j.cca.2014.10.030</doi><tpages>4</tpages></addata></record> |
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| subjects | Abnormalities, Multiple - urine Amidohydrolases - deficiency Amidohydrolases - genetics Amidohydrolases - urine beta-Alanine - analogs & derivatives beta-Alanine - urine Brain Diseases - urine Dravet syndrome Dual molecular diagnoses Epilepsies, Myoclonic - complications Epilepsies, Myoclonic - genetics Epilepsies, Myoclonic - urine Gas Chromatography-Mass Spectrometry - methods Homozygote Humans Infant Magnetic Resonance Spectroscopy - methods Male Movement Disorders - urine NAV1.1 Voltage-Gated Sodium Channel - genetics NMR spectroscopy Purine-Pyrimidine Metabolism, Inborn Errors - urine Urea - analogs & derivatives Urea - urine Urinalysis - methods β-Ureidopropionase deficiency |
| title | NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome |
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