Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria
Abstract Background Expanded carrier screening (ECS) utilizes high‐throughput next‐generation sequencing to evaluate an individual's carrier status for multiple conditions. Combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency is a rare inherited disease included in such...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1621 |
| _version_ | 1797302188727336960 |
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| author | Marie Cosette Gabriel Stephanie M. Rice Jennifer L. Sloan Matthew H. Mossayebi Charles P. Venditti Huda B. Al‐Kouatly |
| author_facet | Marie Cosette Gabriel Stephanie M. Rice Jennifer L. Sloan Matthew H. Mossayebi Charles P. Venditti Huda B. Al‐Kouatly |
| author_sort | Marie Cosette Gabriel |
| collection | DOAJ |
| description | Abstract Background Expanded carrier screening (ECS) utilizes high‐throughput next‐generation sequencing to evaluate an individual's carrier status for multiple conditions. Combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency is a rare inherited disease included in such screening panels. Some cases have been reported with metabolic symptoms in childhood yet other cases describe a benign clinical course, suggesting the clinical phenotype is not well defined. Methods/Case Report Clinical and laboratory findings during the prenatal period were obtained retrospectively from medical records. Results A 37‐year‐old nulliparous woman and her partner were each identified as carriers of ACSF3 variants and presented at 9 weeks gestation for prenatal genetic consultation. The couple received extensive genetic counseling and proceeded with chorionic villus sampling at 11 weeks gestation. Subsequent analysis confirmed that the fetus inherited both parental ACSF variants. The couple was devastated by the results and after reviewing options of pregnancy continuation and termination, they decided to terminate the pregnancy. Following this decision, the patient was diagnosed with acute stress disorder. Conclusion This case highlights how expanded carrier screening adds complexity to reproductive decision‐making. Stronger guidelines and additional research are needed to direct and evaluate the timing, composition, and implementation of ECS panels. |
| first_indexed | 2024-03-07T23:33:11Z |
| format | Article |
| id | doaj.art-17c6e9be84be4b0089b4bddb4ddd3fc2 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:33:11Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-17c6e9be84be4b0089b4bddb4ddd3fc22024-02-20T10:41:15ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-04-0194n/an/a10.1002/mgg3.1621Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduriaMarie Cosette Gabriel0Stephanie M. Rice1Jennifer L. Sloan2Matthew H. Mossayebi3Charles P. Venditti4Huda B. Al‐Kouatly5Department of Obstetrics and Gynecology Cooper University Hospital Camden NJ USADivision of Maternal‐Fetal Medicine Department of Obstetrics and Gynecology Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia PA USANational Human Genome Research InstituteNational Institutes of Health Bethesda MD USADivision of Maternal‐Fetal Medicine Department of Obstetrics and Gynecology Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia PA USANational Human Genome Research InstituteNational Institutes of Health Bethesda MD USADivision of Maternal‐Fetal Medicine Department of Obstetrics and Gynecology Sidney Kimmel Medical College of Thomas Jefferson University Philadelphia PA USAAbstract Background Expanded carrier screening (ECS) utilizes high‐throughput next‐generation sequencing to evaluate an individual's carrier status for multiple conditions. Combined malonic and methylmalonic aciduria (CMAMMA) due to ACSF3 deficiency is a rare inherited disease included in such screening panels. Some cases have been reported with metabolic symptoms in childhood yet other cases describe a benign clinical course, suggesting the clinical phenotype is not well defined. Methods/Case Report Clinical and laboratory findings during the prenatal period were obtained retrospectively from medical records. Results A 37‐year‐old nulliparous woman and her partner were each identified as carriers of ACSF3 variants and presented at 9 weeks gestation for prenatal genetic consultation. The couple received extensive genetic counseling and proceeded with chorionic villus sampling at 11 weeks gestation. Subsequent analysis confirmed that the fetus inherited both parental ACSF variants. The couple was devastated by the results and after reviewing options of pregnancy continuation and termination, they decided to terminate the pregnancy. Following this decision, the patient was diagnosed with acute stress disorder. Conclusion This case highlights how expanded carrier screening adds complexity to reproductive decision‐making. Stronger guidelines and additional research are needed to direct and evaluate the timing, composition, and implementation of ECS panels.https://doi.org/10.1002/mgg3.1621ACSFCMAMMAexpanded carrier screeninggenetic counseling |
| spellingShingle | Marie Cosette Gabriel Stephanie M. Rice Jennifer L. Sloan Matthew H. Mossayebi Charles P. Venditti Huda B. Al‐Kouatly Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria Molecular Genetics & Genomic Medicine ACSF CMAMMA expanded carrier screening genetic counseling |
| title | Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria |
| title_full | Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria |
| title_fullStr | Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria |
| title_full_unstemmed | Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria |
| title_short | Considerations of expanded carrier screening: Lessons learned from combined malonic and methylmalonic aciduria |
| title_sort | considerations of expanded carrier screening lessons learned from combined malonic and methylmalonic aciduria |
| topic | ACSF CMAMMA expanded carrier screening genetic counseling |
| url | https://doi.org/10.1002/mgg3.1621 |
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