Childhood onset dystonia, chorea or related movement disorder
Gene: ASLComment on list classification: Promoting this gene to amber, with a recommendation of green rating subject to GMS review. 6 patients with tremor and/or dystonia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023 and PMID: 28251416 - Baruteau et al 2017).Created: 7 Jan 2024, 3:31 p.m. | Last Modified: 7 Jan 2024, 3:31 p.m.
Panel Version: 3.65
Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.
The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.
PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries, PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient.
More recent retrospectives show that tremors and/or dystonia is reported in some individuals with Argininosuccinic aciduria. 6 cases with ataxia and ASL variant identified are reported.
PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 4 were reported to show tremor/dystonia, with this phenotype present at ages 9, 11, 24 and 25 years of age. Homozygous or compound het ASL variants were recorded in 25/60 patients including 3 out of the 4 patients with tremor/dystonia (patients 4,9 and 25 with c.719-2A>G; c.857A>G, c.1153C>T; c.1153C>T and c.437G>A; c.446+1G>A respectively). Genotype data was not available for other patients. Although patient 4 from this study and patient 9 from the Baruteau et al 2017 study share the same genotype and are both male, their phenotypic descriptions differ so assuming here that they are not the same patient.
PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Tremors or dystonia were reported in 4 individuals (1,4,9 and 25). All were diagnosed before the age of 3 although it is not stated at what age the tremors/dystonia were first noted. The first 3 of these patients had homozygous or compound het variants in ASL identified (c.35G>A;c.35G>A, c.377G>A;c.377G>A and c.719-2A>G, c.857A>G respectively).
(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )Created: 7 Jan 2024, 3:27 p.m. | Last Modified: 7 Jan 2024, 3:59 p.m.
Panel Version: 3.65
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Movement disorders including tremors and dystonia reported in multiple individuals with argininosuccinic aciduria (PMID 38044746, 36994644, 28251416).Created: 8 Dec 2023, 12:32 p.m. | Last Modified: 8 Dec 2023, 12:32 p.m.
Panel Version: 3.56
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Movement disorder; tremor; dystonia
Publications
Tag Q4_23_promote_green tag was added to gene: ASL. Tag Q4_23_NHS_review tag was added to gene: ASL.
Gene: asl has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: ASL was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ASL were changed from to Argininosuccinic aciduria, OMIM:207900; argininosuccinic aciduria, MONDO:0008815; tremor, HP:0001337; Dystonia, HP:0001332
Publications for gene: ASL were set to
gene: ASL was added gene: ASL was added to Childhood onset dystonia or chorea or related movement disorder. Sources: London North GLH,Expert Review Red Mode of inheritance for gene: ASL was set to