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Clinical presentation and genetic variants in patients with autoinflammatory diseases: results from the German GARROD registry

To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who...

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Main Authors: Blank, Norbert (Author) , Kötter, Ina (Author) , Schmalzing, Marc (Author) , Rech, Jürgen (Author) , Krause, Karoline (Author) , Köhler, Birgit (Author) , Kaudewitz, Dorothee (Author) , Nitschke, Martin (Author) , Haas, Christian S. (Author) , Lorenz, Hanns-Martin (Author) , Krusche, Martin (Author)
Format: Article (Journal)
Language:English
Published: 2023
In: Rheumatology international
Year: 2023, Pages: 1-9
ISSN:1437-160X
DOI:10.1007/s00296-023-05443-x
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00296-023-05443-x
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Author Notes:Norbert Blank, Ina Kötter, Marc Schmalzing, Jürgen Rech, Karoline Krause, Birgit Köhler, Dorothee Kaudewitz, Martin Nitschke, Christian S. Haas, Hanns-Martin Lorenz, Martin Krusche
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Summary:To investigate clinical symptoms and genetic variants in patients from the German anti-IL-1 registry for autoinflammatory orphan diseases (GARROD) between 2013 and 2022. Multicentre, retrospective analysis of demographic, clinical and genetic data of patients with autoinflammatory diseases (AID) who received anti-IL-1 targeted therapy. The cohort comprised 152 patients with familial Mediterranean fever (FMF; n = 71), cryopyrin-associated periodic syndromes (CAPS; n = 43), TNF-receptor associated periodic syndrome (TRAPS; n = 19), mevalonate kinase deficiency (MKD; n = 3) and unclassified AID (uAID; n = 16). Inflammatory attacks started in 61.2% of the patients before the age of 18 years. The delay between the first AID attack and anti-IL-1 therapy was 17.8 years. Monogenetic AIDs were diagnosed by clinical symptoms. Genetic analyses confirmed the diagnosis in 87.3% of patients with FMF, 65.2% with CAPS and 94.8% with TRAPS. Among this group, heterozygous MEFV variants and variants of unknown significance (VUS) were detected in 22.5% of patients with FMF, 51.2% with CAPS and 47.4% with TRAPS. Patients with VUS were older at disease onset which is consistent with a milder phenotype. Twenty-four patients had secondary AA amyloidosis (AA) at initiation of anti-IL-1 therapy. The mean age of these patients was 16.4 years at their first attack and 44.9 years at the time of AA diagnosis. Turkish-Armenian ancestry correlated with MEFV variants and higher FMF disease activity compared to German ancestry. Molecular genetic analyses should substantiate the clinical diagnosis of a monogenetic AID. Our data support the concept of variable penetrance of VUS which can be associated with late-onset AID.
Item Description:Online veröffentlicht: 25. September 2023
Gesehen am 14.11.2023
Physical Description:Online Resource
ISSN:1437-160X
DOI:10.1007/s00296-023-05443-x

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