Hereditary ataxia with onset in adulthood

Gene: SPR

Red List (low evidence)

The rating of this gene has been updated to red and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 4:40 p.m. | Last Modified: 11 Mar 2026, 4:40 p.m.

Panel Version: 8.25

Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is also changed from 'Both mono- and biallelic' to 'Biallelic', with a watchlist_moi tag to monitor for more dominant cases.

Created: 13 Mar 2025, 5:01 p.m. | Last Modified: 13 Mar 2025, 5:01 p.m.

Panel Version: 7.13

Signs and symptoms of dopa-responsive dystonia usually appear in infancy or childhood, most commonly around age 6 (PMID: 26131547). Severity of disease can vary and milder symptoms may be overlooked leading to recognition of the disorder in late childhood (PMID: 22522443; 21431957). However, there is no evidence of onset in adulthood.

SPR was classified as Red on the R58 Adult onset neurodegenerative disorder panel following expert review due to the typical age of onset. Therefore, recommending that this gene is downgraded from Green to Red on this panel at the next GMS panel update.

Created: 13 Mar 2025, 4:10 p.m. | Last Modified: 13 Mar 2025, 4:10 p.m.

Panel Version: 7.12

Phenotypes
Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716

Publications

• 26131547

I don't know

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.

Created: 15 Apr 2019, 10:21 a.m.

Green List (high evidence)

Multiple reports in the literature, ataxia listed as part of OMIM phenotype. Single case report of AD disease (milder) associated with a missense variant - not enough to warrant reporting heterozygous variants

Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Dopa-responsive dystonia due to sepiaterin reductase deficiency, 612716