Three “Vitamin B6-Dependent” Newborn Seizure Stories: Why the Gene (ALDH7A1 vs PNPO) Matters

A small case series reports three neonatal epilepsy cases linked to vitamin B6 metabolism genes, reinforcing that early recognition and the right confirmatory testing can change outcomes.

Pyridoxine-dependent epilepsy (PDE) is rare, but it is one of the most important “don’t-miss” causes of neonatal seizures because treatment can be effective. This report adds three more cases to the limited clinical literature, involving pathogenic variants in ALDH7A1 (classic PDE-ALDH7A1) and PNPO (a related vitamin B6-pathway disorder that can also present with early seizures).

The family takeaway is that “B6-responsive seizures” are not one single diagnosis. The underlying gene can influence which form of vitamin B6 biology is disrupted (and therefore which therapies and monitoring strategies clinicians consider), and it also affects what families should expect regarding long-term follow-up.

Scientifically, these disorders converge on PLP availability in the brain. In PDE-ALDH7A1, lysine-pathway metabolites like P6C can inactivate PLP; in PNPO deficiency, the conversion steps needed to generate PLP can be impaired. Both routes can starve PLP-dependent brain enzymes, including those involved in neurotransmitter metabolism. That shared mechanism is why “trial and response” can be dramatic, but it is also why gene-level confirmation matters for long-term management and family planning.

Why this matters

It reinforces a practical message: neonatal seizures with atypical features, poor response to standard antiseizure medicines, or relapse should keep treatable B6-pathway epilepsies high on the differential.

Limitations

This is a small case series. It expands awareness but cannot define how often specific presentations occur or which approach is best for every patient.

Sources

• “Pyridoxine-dependent early onset seizures associated with rare gene mutations: A case series.” Journal of the Pakistan Medical Association (2025). DOI: 10.47391/jpma.20872 (PubMed: 41418146)

Safety note: This summary is educational and not medical advice.