Likely inborn error of metabolism

Gene: GSTZ1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:37 p.m. | Last Modified: 26 Sep 2024, 3:37 p.m.

Panel Version: 6.10

Comment on list classification: As reported in PMID:27876694 and reviewed by Saikat Santra, there are three boys and three girls with maleylacetoacetate isomerase deficiency (MAAID), identified by newborn screening with mildly elevated succinylacetone (SA) by mass spectrometry on dried blood spot.

Four of them were identified with homozygous GSTZ1 variants, one with compound heterozygous variants and one with heterozygous variant.

Hence, there is sufficient evidence available for the association of biallelic GSTZ1 variants with MAAID and this gene can be promoted to green rating in the next GMS review.

Created: 30 Jan 2024, 6:35 p.m. | Last Modified: 30 Jan 2024, 6:35 p.m.

Panel Version: 4.125

Comment on phenotypes: This gene has been associated with maleylacetoacetate isomerase deficiency in OMIM (MIM #617596), but not with any phenotypes in Gene2Phenotype.

Created: 30 Jan 2024, 6:29 p.m. | Last Modified: 30 Jan 2024, 6:29 p.m.

Panel Version: 4.124

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
[Maleylacetoacetate isomerase deficiency], OMIM:617596

Green List (high evidence)

GSTZ1 is established as the molecular cause for maleylacetoacetate isomerase deficiency which is an established inherited metabolic disorder and associated with succinylacetone excretion so may be detected on newborn screening programmes for hereditary tyrosinaemia type1 (FAH). The committee established for developing the pathways for rolling this out recommended that genetic testing for GSTZ1 be made available via the R98 panel to help evaluate patients with mild hypersuccinylacetonaemia - but patients with elevated succinylacetone on routine metabolic testing would also benefit from this being available.
Sources: Literature, Expert Review, Eligibility statement prior genetic testing

Created: 23 Jan 2024, 10:11 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Biochemical: hypersuccinylacetonaemia

Publications

• 27876694