Early onset or syndromic epilepsy

Gene: PNPO

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AR Pyridoxamine 5-phosphate oxidase deficiency (PNPOD). Inborn error of metabolism resulting in vit B6 defic - manifests as neonatal seizures and subsequent encephalopathy. Mills et al, 2005 - 5 patients in 3 families - homozygous missense, splice site and stop codon variants. expression studies done. Plecko et al, 2014 - 11 patients from 7 unrelated families - 3 diff biallelic mutations - 6 of the families (all derived from former Yugoslavia) carry the same hom missense variant R225H - in vitro functional studies done. Ware et al 2014- 2 unrelated boys - 2 diff hom missesne variants. No functional work.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pyridoxamine 5'-phosphate oxidase deficiency, 610090

Publications

• 26535729
• 15772097

Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 6 variants identified in 12 unrelated cases

Created: 21 Jun 2018, 4:16 p.m.

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Red List (low evidence)

Green List (high evidence)

added treatable tag see PMIDs 24266778, 24658933,15772097

Created: 1 Nov 2017, 2:17 p.m.

The disorder is fatal without treatment. Early treatment is important to decrease the chance of long term developmental delays. Some babies with early treatment have developed normally without any intellectual disabilities. There are less than 50 known cases of pyridoxal 5'-phosphate-dependent epilepsy (25296925, 26535729).

Created: 1 Nov 2017, 2:15 p.m.

Phenotypes
Pyridoxamine 5'-phosphate oxidase deficiency, 610090; Neonatal epileptic encephalopathy

Publications

• 24658933
• 28818555
• 22196487
• 21704546
• 25296925
• 26535729
• 15772097
• 24266778, 24658933