Early onset or syndromic epilepsy

Gene: GSS

I don't know

As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber.

Created: 25 Nov 2019, 8:53 p.m. | Last Modified: 25 Nov 2019, 8:53 p.m.

Panel Version: 1.444

PMID:26669244 (Gunduz et al., 2016) report 4 patients with GS deficiency. Case I and Case IV had seizures noted together with homozygous variants (splicing variant in I and p.R125H in IV): Table 1.

Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.

Panel Version: 1.415

Seizures are recorded in OMIM Clinical synopsis for MIM:266130 based on Marstein et al., 1976 (no PubMed).

Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.

Panel Version: 1.415

PMID:15990954 (Njallson et al 2005) summarise the phenotypes of patients with glutathione synthetase deficiency, but don't mention seizures or epilepsy (as noted in review by Tracy Lester).

Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.

Panel Version: 1.415

PMID:11445798 (Ristoff et al,. 2001) examined 28 patients with Glutathione synthetase deficiency (GSSD). Diagnosis was based on metabolic tests. 16/28 had neurological symptoms such as seizures/psychomotor retardation. In 16 patients with severe GS deficiency, 7 had seizures.

Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.

Panel Version: 1.415

PMID:26984560 (Atwal et al. 2016) present a 19 year old female with Glutathione synthetase deficiency (GSSD). She was diagnosed with a mild seizure disorder age 10, and treated with the antiepileptic lamotrigine, which was discontinued once she was seizure free for 5 years. The authors note it is possible her seizures were unrelated to the underlying GSSD.

Created: 21 Nov 2019, 2:13 p.m. | Last Modified: 21 Nov 2019, 2:13 p.m.

Panel Version: 1.415

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Amber.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

I don't know

AR gluathione synthetase deficiency - in severe form as massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia and CNS damage. Njallson et al, 2005 - clinical phenotype evaluated in 41 patients from 33 families - no mention of specific phenotypes with regards to epilepsy. 1 patient in OMIM mentioned as having seizures - Marstein et al, 1976.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutathione synthetase deficiency,266130; Hemolytic anemia due to glutathione synthetase deficiency,231900

Publications

• 26984560

Green List (high evidence)

Comment on'treatable' tag due to information from PMID:15990954 vitamins C and E to boost their antioxidant levels, and bicarbonate to correct metabolic acidosis.

Created: 20 Mar 2017, 11:09 a.m.

Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.

Created: 20 Mar 2017, 11:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutathione synthetase deficiency 266130; Hemolytic anemia due to glutathione synthetase deficiency 231900