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Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation
Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 ind...
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Published in: | The Journal of pediatrics 2017-01, Vol.180, p.200-205.e8 |
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creator | McCrory, Nicholas M., BA Edick, Mathew J., PhD Ahmad, Ayesha, MD Lipinski, Susan, RD Scott Schwoerer, Jessica A., MD Zhai, Shaohui, PhD Justice, Kaitlin, BS Cameron, Cynthia A., PhD Berry, Susan A., MD Pena, Loren D.M., MD, PhD |
description | Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study. |
doi_str_mv | 10.1016/j.jpeds.2016.09.050 |
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Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</description><identifier>ISSN: 0022-3476</identifier><identifier>EISSN: 1097-6833</identifier><identifier>DOI: 10.1016/j.jpeds.2016.09.050</identifier><identifier>PMID: 27776753</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>C3 acylcarnitine ; Female ; Genotype ; history ; Humans ; hyperammonemia ; hyperglycinemia ; Infant ; Infant, Newborn ; longitudinal follow up ; Male ; Metabolism, Inborn Errors - diagnosis ; Metabolism, Inborn Errors - genetics ; natural ; Neonatal Screening - methods ; newborn screening ; nonketotic ; organic acidemia ; Pediatrics ; Propionic Acidemia - diagnosis ; Propionic Acidemia - genetics ; Retrospective Studies ; Time Factors</subject><ispartof>The Journal of pediatrics, 2017-01, Vol.180, p.200-205.e8</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</citedby><cites>FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</cites><orcidid>0000-0003-1253-6454 ; 0000-0002-2673-7145 ; 0000-0003-2149-9894 ; 0000-0001-7970-688X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27776753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCrory, Nicholas M., BA</creatorcontrib><creatorcontrib>Edick, Mathew J., PhD</creatorcontrib><creatorcontrib>Ahmad, Ayesha, MD</creatorcontrib><creatorcontrib>Lipinski, Susan, RD</creatorcontrib><creatorcontrib>Scott Schwoerer, Jessica A., MD</creatorcontrib><creatorcontrib>Zhai, Shaohui, PhD</creatorcontrib><creatorcontrib>Justice, Kaitlin, BS</creatorcontrib><creatorcontrib>Cameron, Cynthia A., PhD</creatorcontrib><creatorcontrib>Berry, Susan A., MD</creatorcontrib><creatorcontrib>Pena, Loren D.M., MD, PhD</creatorcontrib><creatorcontrib>Inborn Errors of Metabolism Collaborative</creatorcontrib><title>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</title><title>The Journal of pediatrics</title><addtitle>J Pediatr</addtitle><description>Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</description><subject>C3 acylcarnitine</subject><subject>Female</subject><subject>Genotype</subject><subject>history</subject><subject>Humans</subject><subject>hyperammonemia</subject><subject>hyperglycinemia</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>longitudinal follow up</subject><subject>Male</subject><subject>Metabolism, Inborn Errors - diagnosis</subject><subject>Metabolism, Inborn Errors - genetics</subject><subject>natural</subject><subject>Neonatal Screening - methods</subject><subject>newborn screening</subject><subject>nonketotic</subject><subject>organic acidemia</subject><subject>Pediatrics</subject><subject>Propionic Acidemia - diagnosis</subject><subject>Propionic Acidemia - genetics</subject><subject>Retrospective Studies</subject><subject>Time Factors</subject><issn>0022-3476</issn><issn>1097-6833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFUsuO0zAUjRCIKQNfgIS8ZNPixHl5wUijUmCkQSA6rC3HvpneEtvBdiv1d_kSnLaMgA0r27rncXV8suxlThc5zes328V2BB0WRXosKF_Qij7KZjnlzbxuGXuczSgtijkrm_oiexbCllLKS0qfZhdF0zR1U7FZ9nPpzCg9BmeJ68kniBunw3S9sRhRDuQ6KPBRojVgI0FLqpYsZYAj6It3IzqLilwr1GBQkpX1bhhAT9C4gaTTOW_Jynvnw9lDdm7AYNKsd97ImCTI-hAiGPIV9iCHQNZ4b7FHJZPpO-x78GBVMk2qd2iAREdWeznsTmRpdRIwY3QmEBnTXhDSusfh8-xJnxThxfm8zL69X90tP85vP3-4WV7fzlWVl3HeN23HJCt417egNW1bzksuZdc2tOmaElTVlopDVfOcsr7ntOyU1nnFeaWaSrPL7OqkO-46A1olfy8HMXo00h-Ekyj-nljciHu3F1XesrKuk8Drs4B3P3YQojCYwh8GacHtgkiwqm6LOmcJyk5Q5V0IHvoHm5yKqR1iK47tEFM7BOUitSOxXv254QPndx0S4O0JACmnPYIXQeGUu0YPKgrt8D8GV__w1YCpHXL4DgcIW7fzNn2ByEUoBBXrqaBTP_OapUxZwX4B6Sjnqg</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>McCrory, Nicholas M., BA</creator><creator>Edick, Mathew J., PhD</creator><creator>Ahmad, Ayesha, MD</creator><creator>Lipinski, Susan, RD</creator><creator>Scott Schwoerer, Jessica A., MD</creator><creator>Zhai, Shaohui, PhD</creator><creator>Justice, Kaitlin, BS</creator><creator>Cameron, Cynthia A., PhD</creator><creator>Berry, Susan A., MD</creator><creator>Pena, Loren D.M., MD, PhD</creator><general>Elsevier Inc</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1253-6454</orcidid><orcidid>https://orcid.org/0000-0002-2673-7145</orcidid><orcidid>https://orcid.org/0000-0003-2149-9894</orcidid><orcidid>https://orcid.org/0000-0001-7970-688X</orcidid></search><sort><creationdate>20170101</creationdate><title>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</title><author>McCrory, Nicholas M., BA ; Edick, Mathew J., PhD ; Ahmad, Ayesha, MD ; Lipinski, Susan, RD ; Scott Schwoerer, Jessica A., MD ; Zhai, Shaohui, PhD ; Justice, Kaitlin, BS ; Cameron, Cynthia A., PhD ; Berry, Susan A., MD ; Pena, Loren D.M., MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>C3 acylcarnitine</topic><topic>Female</topic><topic>Genotype</topic><topic>history</topic><topic>Humans</topic><topic>hyperammonemia</topic><topic>hyperglycinemia</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>longitudinal follow up</topic><topic>Male</topic><topic>Metabolism, Inborn Errors - diagnosis</topic><topic>Metabolism, Inborn Errors - genetics</topic><topic>natural</topic><topic>Neonatal Screening - methods</topic><topic>newborn screening</topic><topic>nonketotic</topic><topic>organic acidemia</topic><topic>Pediatrics</topic><topic>Propionic Acidemia - diagnosis</topic><topic>Propionic Acidemia - genetics</topic><topic>Retrospective Studies</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCrory, Nicholas M., BA</creatorcontrib><creatorcontrib>Edick, Mathew J., PhD</creatorcontrib><creatorcontrib>Ahmad, Ayesha, MD</creatorcontrib><creatorcontrib>Lipinski, Susan, RD</creatorcontrib><creatorcontrib>Scott Schwoerer, Jessica A., MD</creatorcontrib><creatorcontrib>Zhai, Shaohui, PhD</creatorcontrib><creatorcontrib>Justice, Kaitlin, BS</creatorcontrib><creatorcontrib>Cameron, Cynthia A., PhD</creatorcontrib><creatorcontrib>Berry, Susan A., MD</creatorcontrib><creatorcontrib>Pena, Loren D.M., MD, PhD</creatorcontrib><creatorcontrib>Inborn Errors of Metabolism Collaborative</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCrory, Nicholas M., BA</au><au>Edick, Mathew J., PhD</au><au>Ahmad, Ayesha, MD</au><au>Lipinski, Susan, RD</au><au>Scott Schwoerer, Jessica A., MD</au><au>Zhai, Shaohui, PhD</au><au>Justice, Kaitlin, BS</au><au>Cameron, Cynthia A., PhD</au><au>Berry, Susan A., MD</au><au>Pena, Loren D.M., MD, PhD</au><aucorp>Inborn Errors of Metabolism Collaborative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</atitle><jtitle>The Journal of pediatrics</jtitle><addtitle>J Pediatr</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>180</volume><spage>200</spage><epage>205.e8</epage><pages>200-205.e8</pages><issn>0022-3476</issn><eissn>1097-6833</eissn><abstract>Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27776753</pmid><doi>10.1016/j.jpeds.2016.09.050</doi><orcidid>https://orcid.org/0000-0003-1253-6454</orcidid><orcidid>https://orcid.org/0000-0002-2673-7145</orcidid><orcidid>https://orcid.org/0000-0003-2149-9894</orcidid><orcidid>https://orcid.org/0000-0001-7970-688X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | C3 acylcarnitine Female Genotype history Humans hyperammonemia hyperglycinemia Infant Infant, Newborn longitudinal follow up Male Metabolism, Inborn Errors - diagnosis Metabolism, Inborn Errors - genetics natural Neonatal Screening - methods newborn screening nonketotic organic acidemia Pediatrics Propionic Acidemia - diagnosis Propionic Acidemia - genetics Retrospective Studies Time Factors |
title | Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation |
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