Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience
Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis...
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| Veröffentlicht in: | European journal of pediatrics 2022-05, Vol.181 (5), p.1997-2004 |
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| container_end_page | 2004 |
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| container_issue | 5 |
| container_start_page | 1997 |
| container_title | European journal of pediatrics |
| container_volume | 181 |
| creator | Shamriz, Oded Simon, Amos J. Frizinsky, Shirley Lev, Atar Megged, Orli Barel, Ortal Marcus, Nufar Tal, Yuval Somech, Raz Toker, Ori |
| description | Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis of computerized medical records of children ( |
| doi_str_mv | 10.1007/s00431-022-04397-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2626018717</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2626018717</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-3ff7be6e5e4516377d0ca88958a617679c440495ed8d1a16678f6ec8a25e817c3</originalsourceid><addsrcrecordid>eNp9kUtLxTAQhYMovv-ACwm4cVPNtM2j7kR8geBG1yGm02u1bWrSoq7866beq1dcuAg5MN-cGeYQsgfsCBiTx4GxPIOEpWkSRSGTYoVsQp6lCTApVn_pDbIVwhOLTQWodbKRcQDFQW6Sj0vscKgtfXX-eeypCdRQ69q-wRa7wfh3OjjX0Mp5OjwiLWsz61yoA3UV7X3dTsSS_5Kum1SJVW1r7OILJ9G0HZs4J1bQU3zr0U813CFrlWkC7i7-bXJ_cX53dpXc3F5en53eJDaTfEiyqpIPKJBjzkFkUpbMGqUKrowAKWRh85zlBcdSlWBACKkqgVaZlKMCabNtcjj37b17GTEMuq2DxaYxHbox6FSkgoGSICN68Ad9cqPv4naR4jKejrEiUumcst6F4LHSi2toYHqKR8_j0TEe_RWPnpr2F9bjQ4vlT8t3HhHI5kCIpW6Gfjn7H9tP5C6cMQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2657511009</pqid></control><display><type>article</type><title>Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Shamriz, Oded ; Simon, Amos J. ; Frizinsky, Shirley ; Lev, Atar ; Megged, Orli ; Barel, Ortal ; Marcus, Nufar ; Tal, Yuval ; Somech, Raz ; Toker, Ori</creator><creatorcontrib>Shamriz, Oded ; Simon, Amos J. ; Frizinsky, Shirley ; Lev, Atar ; Megged, Orli ; Barel, Ortal ; Marcus, Nufar ; Tal, Yuval ; Somech, Raz ; Toker, Ori</creatorcontrib><description>Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis of computerized medical records of children (<18 years) admitted in the period between 2012 and 2018 at Shaare Zedek Medical Center in Jerusalem and Edmond and Lily Safra Children’s Hospital, Tel-Hashomer Medical Center, in Ramat Gan, Israel. Patients were genetically diagnosed by a complementary immune workup. We identified 5 patients (3 males) from four different families harboring two novel mutations in the complement components C6–C8. Genetic mutations were identified by whole-exome sequencing or by sequencing of the coding exons of a single gene based on the findings in the immune workup. Clinical manifestations consisted of meningitis with or without meningococcemia. The immune workup demonstrated nearly absent levels of CH50, compatible with a complement pathway defect. Diagnosis delay ranged between 0 and 30 years.
Conclusion:
Awareness of risk factors for primary complement deficiencies, even at the first infectious episode, should facilitate prompt immune and genetic workup, commencing diagnosis and proper treatment for the patient and family.
What is Known:
•
Deficiencies in the classical terminal complement components increase susceptibility to invasive meningococcal infections.
•
Recurrent meningococcal infections mandate a diagnostic workup of the complement system.
What is New:
•
Genetic workup can be utilized for prompt diagnosis of complement deficiencies.
•
High rates of consanguinity, even in the presence of a single meningococcal infection, should promote immune and genetic workups.</description><identifier>ISSN: 1432-1076</identifier><identifier>ISSN: 0340-6199</identifier><identifier>EISSN: 1432-1076</identifier><identifier>DOI: 10.1007/s00431-022-04397-9</identifier><identifier>PMID: 35118517</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Child ; Children ; Complement C6 ; Complement C8 - genetics ; Complement system ; Complement System Proteins - genetics ; Consanguinity ; Diagnosis ; Exons ; Female ; Hereditary Complement Deficiency Diseases ; Humans ; Male ; Medical diagnosis ; Medical records ; Medicine ; Medicine & Public Health ; Meningitis ; Meningitis, Meningococcal ; Meningococcal Infections ; Mutation ; Neisseria meningitidis ; Original Article ; Patients ; Pediatrics ; Retrospective Studies ; Risk factors</subject><ispartof>European journal of pediatrics, 2022-05, Vol.181 (5), p.1997-2004</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-3ff7be6e5e4516377d0ca88958a617679c440495ed8d1a16678f6ec8a25e817c3</citedby><cites>FETCH-LOGICAL-c375t-3ff7be6e5e4516377d0ca88958a617679c440495ed8d1a16678f6ec8a25e817c3</cites><orcidid>0000-0002-5248-3193</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00431-022-04397-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00431-022-04397-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35118517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shamriz, Oded</creatorcontrib><creatorcontrib>Simon, Amos J.</creatorcontrib><creatorcontrib>Frizinsky, Shirley</creatorcontrib><creatorcontrib>Lev, Atar</creatorcontrib><creatorcontrib>Megged, Orli</creatorcontrib><creatorcontrib>Barel, Ortal</creatorcontrib><creatorcontrib>Marcus, Nufar</creatorcontrib><creatorcontrib>Tal, Yuval</creatorcontrib><creatorcontrib>Somech, Raz</creatorcontrib><creatorcontrib>Toker, Ori</creatorcontrib><title>Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience</title><title>European journal of pediatrics</title><addtitle>Eur J Pediatr</addtitle><addtitle>Eur J Pediatr</addtitle><description>Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis of computerized medical records of children (<18 years) admitted in the period between 2012 and 2018 at Shaare Zedek Medical Center in Jerusalem and Edmond and Lily Safra Children’s Hospital, Tel-Hashomer Medical Center, in Ramat Gan, Israel. Patients were genetically diagnosed by a complementary immune workup. We identified 5 patients (3 males) from four different families harboring two novel mutations in the complement components C6–C8. Genetic mutations were identified by whole-exome sequencing or by sequencing of the coding exons of a single gene based on the findings in the immune workup. Clinical manifestations consisted of meningitis with or without meningococcemia. The immune workup demonstrated nearly absent levels of CH50, compatible with a complement pathway defect. Diagnosis delay ranged between 0 and 30 years.
Conclusion:
Awareness of risk factors for primary complement deficiencies, even at the first infectious episode, should facilitate prompt immune and genetic workup, commencing diagnosis and proper treatment for the patient and family.
What is Known:
•
Deficiencies in the classical terminal complement components increase susceptibility to invasive meningococcal infections.
•
Recurrent meningococcal infections mandate a diagnostic workup of the complement system.
What is New:
•
Genetic workup can be utilized for prompt diagnosis of complement deficiencies.
•
High rates of consanguinity, even in the presence of a single meningococcal infection, should promote immune and genetic workups.</description><subject>Child</subject><subject>Children</subject><subject>Complement C6</subject><subject>Complement C8 - genetics</subject><subject>Complement system</subject><subject>Complement System Proteins - genetics</subject><subject>Consanguinity</subject><subject>Diagnosis</subject><subject>Exons</subject><subject>Female</subject><subject>Hereditary Complement Deficiency Diseases</subject><subject>Humans</subject><subject>Male</subject><subject>Medical diagnosis</subject><subject>Medical records</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meningitis</subject><subject>Meningitis, Meningococcal</subject><subject>Meningococcal Infections</subject><subject>Mutation</subject><subject>Neisseria meningitidis</subject><subject>Original Article</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Retrospective Studies</subject><subject>Risk factors</subject><issn>1432-1076</issn><issn>0340-6199</issn><issn>1432-1076</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtLxTAQhYMovv-ACwm4cVPNtM2j7kR8geBG1yGm02u1bWrSoq7866beq1dcuAg5MN-cGeYQsgfsCBiTx4GxPIOEpWkSRSGTYoVsQp6lCTApVn_pDbIVwhOLTQWodbKRcQDFQW6Sj0vscKgtfXX-eeypCdRQ69q-wRa7wfh3OjjX0Mp5OjwiLWsz61yoA3UV7X3dTsSS_5Kum1SJVW1r7OILJ9G0HZs4J1bQU3zr0U813CFrlWkC7i7-bXJ_cX53dpXc3F5en53eJDaTfEiyqpIPKJBjzkFkUpbMGqUKrowAKWRh85zlBcdSlWBACKkqgVaZlKMCabNtcjj37b17GTEMuq2DxaYxHbox6FSkgoGSICN68Ad9cqPv4naR4jKejrEiUumcst6F4LHSi2toYHqKR8_j0TEe_RWPnpr2F9bjQ4vlT8t3HhHI5kCIpW6Gfjn7H9tP5C6cMQ</recordid><startdate>20220501</startdate><enddate>20220501</enddate><creator>Shamriz, Oded</creator><creator>Simon, Amos J.</creator><creator>Frizinsky, Shirley</creator><creator>Lev, Atar</creator><creator>Megged, Orli</creator><creator>Barel, Ortal</creator><creator>Marcus, Nufar</creator><creator>Tal, Yuval</creator><creator>Somech, Raz</creator><creator>Toker, Ori</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature 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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5248-3193</orcidid></search><sort><creationdate>20220501</creationdate><title>Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience</title><author>Shamriz, Oded ; Simon, Amos J. ; Frizinsky, Shirley ; Lev, Atar ; Megged, Orli ; Barel, Ortal ; Marcus, Nufar ; Tal, Yuval ; Somech, Raz ; Toker, Ori</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-3ff7be6e5e4516377d0ca88958a617679c440495ed8d1a16678f6ec8a25e817c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Child</topic><topic>Children</topic><topic>Complement C6</topic><topic>Complement C8 - genetics</topic><topic>Complement system</topic><topic>Complement System Proteins - genetics</topic><topic>Consanguinity</topic><topic>Diagnosis</topic><topic>Exons</topic><topic>Female</topic><topic>Hereditary Complement Deficiency Diseases</topic><topic>Humans</topic><topic>Male</topic><topic>Medical diagnosis</topic><topic>Medical records</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Meningitis</topic><topic>Meningitis, Meningococcal</topic><topic>Meningococcal Infections</topic><topic>Mutation</topic><topic>Neisseria meningitidis</topic><topic>Original Article</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Retrospective Studies</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shamriz, Oded</creatorcontrib><creatorcontrib>Simon, Amos J.</creatorcontrib><creatorcontrib>Frizinsky, Shirley</creatorcontrib><creatorcontrib>Lev, Atar</creatorcontrib><creatorcontrib>Megged, Orli</creatorcontrib><creatorcontrib>Barel, Ortal</creatorcontrib><creatorcontrib>Marcus, Nufar</creatorcontrib><creatorcontrib>Tal, Yuval</creatorcontrib><creatorcontrib>Somech, Raz</creatorcontrib><creatorcontrib>Toker, Ori</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shamriz, Oded</au><au>Simon, Amos J.</au><au>Frizinsky, Shirley</au><au>Lev, Atar</au><au>Megged, Orli</au><au>Barel, Ortal</au><au>Marcus, Nufar</au><au>Tal, Yuval</au><au>Somech, Raz</au><au>Toker, Ori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience</atitle><jtitle>European journal of pediatrics</jtitle><stitle>Eur J Pediatr</stitle><addtitle>Eur J Pediatr</addtitle><date>2022-05-01</date><risdate>2022</risdate><volume>181</volume><issue>5</issue><spage>1997</spage><epage>2004</epage><pages>1997-2004</pages><issn>1432-1076</issn><issn>0340-6199</issn><eissn>1432-1076</eissn><abstract>Diagnosis of primary complement deficiencies requires a high index of suspicion. Thus, susceptible patients are often underdiagnosed and untreated. Here, we present a multicenter experience with two novel inborn errors of the classical complement system. This is a retrospective multicenter analysis of computerized medical records of children (<18 years) admitted in the period between 2012 and 2018 at Shaare Zedek Medical Center in Jerusalem and Edmond and Lily Safra Children’s Hospital, Tel-Hashomer Medical Center, in Ramat Gan, Israel. Patients were genetically diagnosed by a complementary immune workup. We identified 5 patients (3 males) from four different families harboring two novel mutations in the complement components C6–C8. Genetic mutations were identified by whole-exome sequencing or by sequencing of the coding exons of a single gene based on the findings in the immune workup. Clinical manifestations consisted of meningitis with or without meningococcemia. The immune workup demonstrated nearly absent levels of CH50, compatible with a complement pathway defect. Diagnosis delay ranged between 0 and 30 years.
Conclusion:
Awareness of risk factors for primary complement deficiencies, even at the first infectious episode, should facilitate prompt immune and genetic workup, commencing diagnosis and proper treatment for the patient and family.
What is Known:
•
Deficiencies in the classical terminal complement components increase susceptibility to invasive meningococcal infections.
•
Recurrent meningococcal infections mandate a diagnostic workup of the complement system.
What is New:
•
Genetic workup can be utilized for prompt diagnosis of complement deficiencies.
•
High rates of consanguinity, even in the presence of a single meningococcal infection, should promote immune and genetic workups.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35118517</pmid><doi>10.1007/s00431-022-04397-9</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5248-3193</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1432-1076 |
| ispartof | European journal of pediatrics, 2022-05, Vol.181 (5), p.1997-2004 |
| issn | 1432-1076 0340-6199 1432-1076 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2626018717 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Child Children Complement C6 Complement C8 - genetics Complement system Complement System Proteins - genetics Consanguinity Diagnosis Exons Female Hereditary Complement Deficiency Diseases Humans Male Medical diagnosis Medical records Medicine Medicine & Public Health Meningitis Meningitis, Meningococcal Meningococcal Infections Mutation Neisseria meningitidis Original Article Patients Pediatrics Retrospective Studies Risk factors |
| title | Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience |
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