Hereditary neuropathy or pain disorder

Gene: ETFDH

Green List (high evidence)

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

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Acyl-CoA dehydrogenase deficiency associated with peripheral neuropathy has been associated with ETFDH variants (PMID: 30587156;26205240;32608139;26821934). At least eleven ETFDH variants have been reported in at least nine unrelated cases.

Created: 4 Nov 2024, 6:13 p.m. | Last Modified: 4 Nov 2024, 6:13 p.m.

Panel Version: 6.75

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - minor feature / Broader phenotype: Glutaric acidemia IIc - minor feature

Created: 6 Dec 2019, 7:57 p.m. | Last Modified: 6 Dec 2019, 7:57 p.m.

Panel Version: 0.52

Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 7:56 p.m. | Last Modified: 6 Dec 2019, 7:56 p.m.

Panel Version: 0.52

Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

Green List (high evidence)

multiple families with neuropathy as part of syndrome, Now R78 includes complex phenotypes should be included

Created: 20 Oct 2024, 9:46 a.m. | Last Modified: 20 Oct 2024, 9:46 a.m.

Panel Version: 5.19

Reported in case series but always a minor component of the disease

Created: 6 Jun 2019, 10:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Neonatal and late onset forms. hypoglycaemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occur. Riboflavin responsive.

Publications

• 32608139: 26821934: 0587156