Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants
(2023) In Genetics in Medicine 25(6).- Abstract
- Purpose: The study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and to determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied through an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 48 (likely) pathogenic TRMU variants, of which, 18 were novel. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals,... (More)
- Purpose: The study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and to determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied through an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 48 (likely) pathogenic TRMU variants, of which, 18 were novel. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals, 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. Conclusion: In most patients, TRMU-associated ALF is a transient, reversible disease and cysteine supplementation improved survival. © 2022 The Authors (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/f738aa74-01f8-42f1-8a11-53983e3a0550
- author
- Vogel, G.F. ; Eklund, E.A. LU and Wortmann, S.
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acute liver failure, Cysteine, Liver transplantation, Mitochondrial disease, Treatment
- in
- Genetics in Medicine
- volume
- 25
- issue
- 6
- article number
- 100314
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85140967450
- pmid:36305855
- ISSN
- 1098-3600
- DOI
- 10.1016/j.gim.2022.09.015
- language
- English
- LU publication?
- yes
- id
- f738aa74-01f8-42f1-8a11-53983e3a0550
- date added to LUP
- 2023-01-11 13:45:46
- date last changed
- 2023-10-26 14:54:26
@article{f738aa74-01f8-42f1-8a11-53983e3a0550,
abstract = {{Purpose: The study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and to determine the role of cysteine supplementation in its treatment. Methods: Individuals with biallelic (likely) pathogenic variants in TRMU were studied through an international retrospective collection of de-identified patient data. Results: In 62 individuals, including 30 previously unreported cases, we described 48 (likely) pathogenic TRMU variants, of which, 18 were novel. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals, 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. Conclusion: In most patients, TRMU-associated ALF is a transient, reversible disease and cysteine supplementation improved survival. © 2022 The Authors}},
author = {{Vogel, G.F. and Eklund, E.A. and Wortmann, S.}},
issn = {{1098-3600}},
keywords = {{Acute liver failure; Cysteine; Liver transplantation; Mitochondrial disease; Treatment}},
language = {{eng}},
number = {{6}},
publisher = {{Nature Publishing Group}},
series = {{Genetics in Medicine}},
title = {{Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants}},
url = {{http://dx.doi.org/10.1016/j.gim.2022.09.015}},
doi = {{10.1016/j.gim.2022.09.015}},
volume = {{25}},
year = {{2023}},
}