Likely inborn error of metabolism

Gene: SLC52A3

Green List (high evidence)

Comment on mode of inheritance: There is evidence available for the association of both monoallelic and biallelic variants in this gene to riboflavin transporter deficiency. The MOI of this gene has already been set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/SLC52A3/) Hence, the MOI should be updated to BOTH on this panel.

Created: 20 Mar 2026, 5:12 p.m. | Last Modified: 20 Mar 2026, 5:12 p.m.

Panel Version: 8.103

There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194)

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Variant in only one allele was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
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PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.

Created: 20 Mar 2026, 5:01 p.m. | Last Modified: 20 Mar 2026, 5:28 p.m.

Panel Version: 8.103

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Brown-Vialetto-Van Laere syndrome 1, OMIM:211530; Brown-Vialetto-van Laere syndrome 1, MONDO:0024537; ?Fazio-Londe disease, OMIM:211500; riboflavin transporter deficiency, MONDO:0008891

Publications

• 22718020
• 29053833
• 34384672
• 38469093
• 40539137

Red List (low evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.

Created: 23 Jul 2019, 10:13 a.m. | Last Modified: 23 Jul 2019, 10:13 a.m.

Panel Version: 1.412