Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus
BackgroundAutoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Pediatrics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2023.1150179/full |
| _version_ | 1797843770928005120 |
|---|---|
| author | Fawzia M. Elgharbawy Fawzia M. Elgharbawy Mohammed Yousuf Karim Mohammed Yousuf Karim Dina Sameh Soliman Dina Sameh Soliman Amel Siddik Hassan Anoop Sudarsanan Ashraf Gad Ashraf Gad |
| author_facet | Fawzia M. Elgharbawy Fawzia M. Elgharbawy Mohammed Yousuf Karim Mohammed Yousuf Karim Dina Sameh Soliman Dina Sameh Soliman Amel Siddik Hassan Anoop Sudarsanan Ashraf Gad Ashraf Gad |
| author_sort | Fawzia M. Elgharbawy |
| collection | DOAJ |
| description | BackgroundAutoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.Case presentationWe herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.ConclusionWe described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms. |
| first_indexed | 2024-04-09T17:11:18Z |
| format | Article |
| id | doaj.art-45f5f143421a4ddcbaaee707258ad727 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-04-09T17:11:18Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-45f5f143421a4ddcbaaee707258ad7272023-04-20T05:55:30ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-04-011110.3389/fped.2023.11501791150179Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimusFawzia M. Elgharbawy0Fawzia M. Elgharbawy1Mohammed Yousuf Karim2Mohammed Yousuf Karim3Dina Sameh Soliman4Dina Sameh Soliman5Amel Siddik Hassan6Anoop Sudarsanan7Ashraf Gad8Ashraf Gad9Neonatal Intensive Care Unit, Department of Pediatrics, AL Wakra Hospital, Hamad Medical Corporation, Doha, QatarWeill Cornell Medicine- Qatar (WCM-Q), Cornell University, Doha, QatarImmunopathology Section, Sidra Medicine, Doha, QatarCollege of Medicine, Qatar University, Doha, QatarWeill Cornell Medicine- Qatar (WCM-Q), Cornell University, Doha, QatarDepartment of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, QatarAllergy and Immunology section, Department of Pediatrics, Sidra Medicine, Doha, QatarNeonatal Intensive Care Unit, Women's Wellness and Research Center, Hamad Medical Corporation, Doha, QatarWeill Cornell Medicine- Qatar (WCM-Q), Cornell University, Doha, QatarNeonatal Intensive Care Unit, Women's Wellness and Research Center, Hamad Medical Corporation, Doha, QatarBackgroundAutoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of “double-negative” T-cells (DNTs) (T-cell receptor αβ+ CD4−CD8−) and an increased risk of developing malignancies later in life.Case presentationWe herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs.ConclusionWe described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.https://www.frontiersin.org/articles/10.3389/fped.2023.1150179/fullALPS (autoimmune lymphoproliferative syndrome)DNT-cellssirolimusFASnovel variantnewborn |
| spellingShingle | Fawzia M. Elgharbawy Fawzia M. Elgharbawy Mohammed Yousuf Karim Mohammed Yousuf Karim Dina Sameh Soliman Dina Sameh Soliman Amel Siddik Hassan Anoop Sudarsanan Ashraf Gad Ashraf Gad Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus Frontiers in Pediatrics ALPS (autoimmune lymphoproliferative syndrome) DNT-cells sirolimus FAS novel variant newborn |
| title | Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus |
| title_full | Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus |
| title_fullStr | Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus |
| title_full_unstemmed | Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus |
| title_short | Case report: Neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous FAS variant effectively treated with sirolimus |
| title_sort | case report neonatal autoimmune lymphoproliferative syndrome with a novel pathogenic homozygous fas variant effectively treated with sirolimus |
| topic | ALPS (autoimmune lymphoproliferative syndrome) DNT-cells sirolimus FAS novel variant newborn |
| url | https://www.frontiersin.org/articles/10.3389/fped.2023.1150179/full |
| work_keys_str_mv | AT fawziamelgharbawy casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT fawziamelgharbawy casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT mohammedyousufkarim casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT mohammedyousufkarim casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT dinasamehsoliman casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT dinasamehsoliman casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT amelsiddikhassan casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT anoopsudarsanan casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT ashrafgad casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus AT ashrafgad casereportneonatalautoimmunelymphoproliferativesyndromewithanovelpathogenichomozygousfasvarianteffectivelytreatedwithsirolimus |