Liver Disease and Risk of Hepatocellular Carcinoma in Children With Mutations in TALDO1
© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases..
Mutations in the transaldolase 1 (TALDO1) gene have been described in a limited number of cases. Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. We report 4 patients presenting with liver disease: 2 with early-onset hepatocellular carcinoma (HCC). Patients with cholestasis and mutations in TALDO1 were identified by next-generation sequencing. Clinical, laboratory, and histological data were collected. Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2-210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). The diagnosis was corroborated by detection of minimal transaldolase enzyme activity in skin fibroblasts in two cases and raised urine polyols in the third. Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha-fetoprotein. Median follow-up was 4 years (range, 1-21). Conclusion: Transaldolase deficiency can include early-onset normal gamma-glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early-onset HCC and may require early LT.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Hepatology communications - 6(2022), 3 vom: 06. März, Seite 473-479 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Grammatikopoulos, Tassos [VerfasserIn] |
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| Anmerkungen: |
Date Completed 02.05.2022 Date Revised 08.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/hep4.1824 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM332171620 |
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| 520 | |a Mutations in the transaldolase 1 (TALDO1) gene have been described in a limited number of cases. Several organs can be affected and clinical manifestations are variable, but often include liver dysfunction and/or hepatosplenomegaly. We report 4 patients presenting with liver disease: 2 with early-onset hepatocellular carcinoma (HCC). Patients with cholestasis and mutations in TALDO1 were identified by next-generation sequencing. Clinical, laboratory, and histological data were collected. Four (1 male) patients were identified with variants predicted to be damaging in TALDO1. Three patients were homozygous (two protein truncating/one missense mutations), 1 one was compound heterozygous (two missense mutations). Median age at presentation was 4 months (range, 2-210 days) with jaundice (3), hepatosplenomegaly (3), and pancytopaenia (1). The diagnosis was corroborated by detection of minimal transaldolase enzyme activity in skin fibroblasts in two cases and raised urine polyols in the third. Three patients underwent liver transplantation (LT), 2 of whom had confirmed HCC on explanted liver. One patient suddenly died shortly after LT. The nontransplanted case has a chronic liver disease with multiple dysplastic liver nodules, but normal liver biochemistry and alpha-fetoprotein. Median follow-up was 4 years (range, 1-21). Conclusion: Transaldolase deficiency can include early-onset normal gamma-glutamyltransferase liver disease with multisystem involvement and variable progression. Patients with this disease are at risk of early-onset HCC and may require early LT | ||
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| 700 | 1 | |a Samyn, Marianne |e verfasserin |4 aut | |
| 700 | 1 | |a Vara, Roshni |e verfasserin |4 aut | |
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| 700 | 1 | |a Hertecant, Jozef |e verfasserin |4 aut | |
| 700 | 1 | |a Al Jasmi, Fatma |e verfasserin |4 aut | |
| 700 | 1 | |a Rahman, Obydur |e verfasserin |4 aut | |
| 700 | 1 | |a Deheragoda, Maesha |e verfasserin |4 aut | |
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| 700 | 1 | |a Thompson, Richard J |e verfasserin |4 aut | |
| 700 | 0 | |a University of Washington Center for Mendelian Genomics |e verfasserin |4 aut | |
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