Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review
Abstract Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic dis...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00404-0 |
| _version_ | 1827326668148047872 |
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| author | Stephen F. Kingsmore Russell Nofsinger Kasia Ellsworth |
| author_facet | Stephen F. Kingsmore Russell Nofsinger Kasia Ellsworth |
| author_sort | Stephen F. Kingsmore |
| collection | DOAJ |
| description | Abstract Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, and net healthcare costs were reduced by $14,265 per child tested by URGS, RGS, or RES. URGS outperformed RGS and RES with faster time to diagnosis, and higher rate of diagnosis and clinical utility. Diagnostic and clinical outcomes will improve as methods evolve, costs decrease, and testing is implemented within precision medicine delivery systems attuned to ICU needs. URGS, RGS, and RES are currently performed in <5% of the ~200,000 children likely to benefit annually due to lack of payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition of possible genetic diseases, and current formatting as tests rather than as a rapid precision medicine delivery system. The gap between actual and optimal outcomes in children in ICUs is currently increasing since expanded use of URGS, RGS, and RES lags growth in those likely to benefit through new therapies. There is sufficient evidence to conclude that URGS, RGS, or RES should be considered in all children with diseases of uncertain etiology at ICU admission. Minimally, diagnostic URGS, RGS, or RES should be ordered early during admissions of critically ill infants and children with suspected genetic diseases. |
| first_indexed | 2024-03-07T14:48:54Z |
| format | Article |
| id | doaj.art-bb362eac87bb4847b1dbc6dcc5f0c4e4 |
| institution | Directory Open Access Journal |
| issn | 2056-7944 |
| language | English |
| last_indexed | 2024-03-07T14:48:54Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj.art-bb362eac87bb4847b1dbc6dcc5f0c4e42024-03-05T19:50:05ZengNature Portfolionpj Genomic Medicine2056-79442024-02-019111410.1038/s41525-024-00404-0Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a reviewStephen F. Kingsmore0Russell Nofsinger1Kasia Ellsworth2Rady Children’s Institute for Genomic Medicine, Rady Children’s HospitalRady Children’s Institute for Genomic Medicine, Rady Children’s HospitalRady Children’s Institute for Genomic Medicine, Rady Children’s HospitalAbstract Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, and net healthcare costs were reduced by $14,265 per child tested by URGS, RGS, or RES. URGS outperformed RGS and RES with faster time to diagnosis, and higher rate of diagnosis and clinical utility. Diagnostic and clinical outcomes will improve as methods evolve, costs decrease, and testing is implemented within precision medicine delivery systems attuned to ICU needs. URGS, RGS, and RES are currently performed in <5% of the ~200,000 children likely to benefit annually due to lack of payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition of possible genetic diseases, and current formatting as tests rather than as a rapid precision medicine delivery system. The gap between actual and optimal outcomes in children in ICUs is currently increasing since expanded use of URGS, RGS, and RES lags growth in those likely to benefit through new therapies. There is sufficient evidence to conclude that URGS, RGS, or RES should be considered in all children with diseases of uncertain etiology at ICU admission. Minimally, diagnostic URGS, RGS, or RES should be ordered early during admissions of critically ill infants and children with suspected genetic diseases.https://doi.org/10.1038/s41525-024-00404-0 |
| spellingShingle | Stephen F. Kingsmore Russell Nofsinger Kasia Ellsworth Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review npj Genomic Medicine |
| title | Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review |
| title_full | Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review |
| title_fullStr | Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review |
| title_full_unstemmed | Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review |
| title_short | Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review |
| title_sort | rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units a review |
| url | https://doi.org/10.1038/s41525-024-00404-0 |
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