Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry
Abstract Background Telomere biology disorders (TBD) such as dyskeratosis congenita (DKC) lead to progressive multi-organ failure as impaired telomere maintenance disturbs cellular proliferative capacity. A wide range of hepatic manifestations from asymptomatic liver enzyme elevation to overt liver...
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-021-02024-8 |
| _version_ | 1818717217898889216 |
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| author | Mareike Tometten Martin Kirschner Susanne Isfort Marie-Luise Berres Tim H. Brümmendorf Fabian Beier |
| author_facet | Mareike Tometten Martin Kirschner Susanne Isfort Marie-Luise Berres Tim H. Brümmendorf Fabian Beier |
| author_sort | Mareike Tometten |
| collection | DOAJ |
| description | Abstract Background Telomere biology disorders (TBD) such as dyskeratosis congenita (DKC) lead to progressive multi-organ failure as impaired telomere maintenance disturbs cellular proliferative capacity. A wide range of hepatic manifestations from asymptomatic liver enzyme elevation to overt liver fibrosis/cirrhosis can be observed in TBD patients. However, the incidence of hepatic involvement remains unknown. Non-invasive transient elastography (TE) predicts early fibrosis by measuring liver stiffness and may uncover subclinical liver damage in TBD patients. Methods Liver screening procedures of nine TBD patients from the Aachen TBD Registry are being presented retrospectively. Following clinical suspicion, TBD was diagnosed using flow-FISH with telomere length (TL) below the 1% percentile and confirmed by next-generation sequencing (NGS) detecting pathogenic mutations in telomere maintenance genes TERC or TERT. Results In all patients, TBD was first diagnosed in adulthood. Patients showed normal to slightly elevated liver function test parameters. Hepatic ultrasound revealed inhomogeneous parenchyma in seven (77.7%) and increased liver echogenicity in four patients (44.4%). Median liver stiffness was 10.7 kilopascal (kPa) (interquartile range 8.4, 15.7 kPa). Using 7.1 kPa as cut-off, 88.8% of patients were classified as moderate fibrosis to cirrhosis. Conclusion Subclinical chronic liver involvement is frequent in patients with adult-onset TBD. TE could have a valuable role in the routine work-up of patients with telomere disorders including DKC for early detection of patients at risk for liver function impairment. |
| first_indexed | 2024-12-17T19:31:39Z |
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| id | doaj.art-7bd7c03c31764661b8ab5c9d985be523 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-17T19:31:39Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-7bd7c03c31764661b8ab5c9d985be5232022-12-21T21:35:14ZengBMCOrphanet Journal of Rare Diseases1750-11722021-09-011611710.1186/s13023-021-02024-8Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registryMareike Tometten0Martin Kirschner1Susanne Isfort2Marie-Luise Berres3Tim H. Brümmendorf4Fabian Beier5Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen UniversityDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen UniversityDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen UniversityCenter for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD)Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen UniversityDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen UniversityAbstract Background Telomere biology disorders (TBD) such as dyskeratosis congenita (DKC) lead to progressive multi-organ failure as impaired telomere maintenance disturbs cellular proliferative capacity. A wide range of hepatic manifestations from asymptomatic liver enzyme elevation to overt liver fibrosis/cirrhosis can be observed in TBD patients. However, the incidence of hepatic involvement remains unknown. Non-invasive transient elastography (TE) predicts early fibrosis by measuring liver stiffness and may uncover subclinical liver damage in TBD patients. Methods Liver screening procedures of nine TBD patients from the Aachen TBD Registry are being presented retrospectively. Following clinical suspicion, TBD was diagnosed using flow-FISH with telomere length (TL) below the 1% percentile and confirmed by next-generation sequencing (NGS) detecting pathogenic mutations in telomere maintenance genes TERC or TERT. Results In all patients, TBD was first diagnosed in adulthood. Patients showed normal to slightly elevated liver function test parameters. Hepatic ultrasound revealed inhomogeneous parenchyma in seven (77.7%) and increased liver echogenicity in four patients (44.4%). Median liver stiffness was 10.7 kilopascal (kPa) (interquartile range 8.4, 15.7 kPa). Using 7.1 kPa as cut-off, 88.8% of patients were classified as moderate fibrosis to cirrhosis. Conclusion Subclinical chronic liver involvement is frequent in patients with adult-onset TBD. TE could have a valuable role in the routine work-up of patients with telomere disorders including DKC for early detection of patients at risk for liver function impairment.https://doi.org/10.1186/s13023-021-02024-8Telomere biology disorderDyskeratosis congenitalTransient elastographyLiver |
| spellingShingle | Mareike Tometten Martin Kirschner Susanne Isfort Marie-Luise Berres Tim H. Brümmendorf Fabian Beier Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry Orphanet Journal of Rare Diseases Telomere biology disorder Dyskeratosis congenital Transient elastography Liver |
| title | Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry |
| title_full | Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry |
| title_fullStr | Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry |
| title_full_unstemmed | Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry |
| title_short | Transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis: a retrospective analysis of the Aachen telomere biology disease registry |
| title_sort | transient elastography in adult patients with cryptic dyskeratosis congenita reveals subclinical liver fibrosis a retrospective analysis of the aachen telomere biology disease registry |
| topic | Telomere biology disorder Dyskeratosis congenital Transient elastography Liver |
| url | https://doi.org/10.1186/s13023-021-02024-8 |
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