Possible mitochondrial disorder - nuclear genes

Gene: BTD

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green. ClinGen mitochondrial gene curation expert panel classified the association between BTD and Leigh syndrome as Moderate. Biotinidase deficiency leads to deficiency of a number of carboxylases including pyruvate carboxylase (PC) and PC is also a green gene on this panel.

Created: 12 Dec 2025, 11 a.m. | Last Modified: 20 Jan 2026, 11:08 a.m.

Panel Version: 4.19

I don't know

Zornitza Stark (Australian Genomics) has rated BTD red on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/BTD/) and has requested that the association between BTD variants and mitochondrial disease could be reviewed.

This gene has been demoted to amber in Mitochondrial disorders panel after being reviewed and agreed by the NHS Genomic Medicine Service. Hence, this gene is now recommended for demotion to amber on this panel and opinion is being sought from the NHS mitochondrial specialist teams on this.

Created: 6 Jun 2025, 9:49 a.m. | Last Modified: 6 Jun 2025, 9:52 a.m.

Panel Version: 4.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Hi
Could this gene be included in the optic neuropathy panel R41 as it is reported to be related to optic neuropathy, potentially a treatable form of optic neuropathy.
Please find some relevant references below:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750409/
https://pubmed.ncbi.nlm.nih.gov/26358973/
https://pubmed.ncbi.nlm.nih.gov/26203071/
https://pubmed.ncbi.nlm.nih.gov/29025919/
https://pubmed.ncbi.nlm.nih.gov/32235217/
Thank you
Kind regards

Mohamed Nassr

Created: 12 Feb 2024, 4:16 p.m. | Last Modified: 12 Feb 2024, 4:16 p.m.

Panel Version: 3.87

Green List (high 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: 4 Feb 2019, 1:36 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Biotinidase deficiency, 253260

Red List (low evidence)

Definitely a green gene for a metabolic disorder, but link to mitochondrial disease?

Created: 27 Aug 2018, 9:50 a.m.

Comment on list classification: Suggested by reviewer Shamima Rahman (UCL Institute of Child Health) and is a confirmed DD gene for Biotinidase deficiency.

Created: 2 Mar 2016, 2:37 p.m.