Adult onset neurodegenerative disorder

Gene: SPR

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 updating the MOI from 'Both mono- and biallelic' to 'Biallelic'

Created: 13 Mar 2025, 4:59 p.m. | Last Modified: 13 Mar 2025, 4:59 p.m.

Panel Version: 7.12

Red List (low evidence)

Evidence supports AR inheritance in the majority - most patients showed onset of neurologic symptoms in infancy or childhood. Red

Created: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.

Panel Version: 1.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
paediatric form of dopa responsive dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Dopa-Responsive Dystonia

Red List (low evidence)

Onset in infancy

Created: 23 Jul 2019, 3:35 p.m. | Last Modified: 23 Jul 2019, 3:35 p.m.

Panel Version: 1.72

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
paediatric form of dopa responsive dystonia; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Dopa-Responsive Dystonia

Red List (low evidence)

As discussed with the GMS Neurology Specialist Test Group webex call 11th September 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red

Created: 20 Sep 2019, 4:19 p.m. | Last Modified: 20 Sep 2019, 4:19 p.m.

Panel Version: 1.106

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. All the green and amber, except for the genes with triplet repeats, were reviewed.

Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.

Panel Version: 1.101

Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.

Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.

Panel Version: 1.74

Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.

Created: 23 Apr 2019, 5:35 p.m.

Red List (low evidence)