Likely inborn error of metabolism

Gene: SLC13A3

Green List (high evidence)

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

Created: 25 Feb 2025, 9:09 a.m. | Last Modified: 25 Feb 2025, 9:09 a.m.

Panel Version: 7.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Comment on list classification: This gene is associated with a relevant phenotype in OMIM (MIM# 618384). At least 9 unrelated cases with biallelic variants in this gene and acute reversible leukoencephalopathy with increased urinary α-ketoglutarate, arising in the context of a febrile illness (PMID: 30635937; 34966709; 35527102; 37290914; 38235040).

Sufficient evidence to promote SLC13A3 to Green at the next GMS panel update.

Created: 13 Nov 2024, 3:20 p.m. | Last Modified: 13 Nov 2024, 3:20 p.m.

Panel Version: 8.6

Green List (high evidence)

Based on the literature SLC13A3 gene variants cause acute reversible leukoencephalopathy and alpha-ketoglutarate accumulation. Patient had hypotonia, abnormal movements, and dysarthria associated with white matter abnormalities and increased urinary alpha-ketoglutarate and NAA. CSF analysis showed increased lactate. Laboratory studies showed increased urinary excretion of alpha-ketoglutarate, succinate, fumarate, and N-acetylaspartate (NAA). These organic acids were also increased in the cerebrospinal fluid (CSF).

The SLC13A3 gene is included an international classification of inherited metabolic disorders (ICIMD), Disorders of the Krebs cycle.
Sources: Literature

Created: 21 Jul 2021, 7:51 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sodium dicarboxylate cotransporter 3 deficiency; Increased urinary dicarboxylic acids, alpha-ketoglutarate, fumarate, N-acetylaspartate; Encephalopathy; Ataxia

Publications

• PMID: 33340416
• PMID: 30635937