Neurogenetics Reference Lab · Teaching Example
- Panel
- Neonatal Epilepsy Panel (95 genes)
- Report ID
- TEACH-0009
- Indication
- Neonatal-onset refractory seizures responsive to pyridoxine; suspected pyridoxine-dependent epilepsy.
- Specimen
- Peripheral blood, EDTA · Received 2026-03-10
- Reported
- 2026-03-28
- Methodology
- Targeted capture NGS, mean depth 240×. Parental Sanger confirmed for phase.
Patient (anonymized teaching example)
Age 6 weeks · Female · European ancestry
Clinical: Refractory seizures from day 2 of life, dramatic and sustained response to IV pyridoxine. Elevated CSF and plasma α-aminoadipic semialdehyde (α-AASA) — biochemically consistent with PDE-ALDH7A1.
Reportable Variants
| Gene | Variant | Zygosity | Condition (Mode) | Origin | Classification |
|---|---|---|---|---|---|
in trans with row 2 | Heterozygous | Pyridoxine-dependent epilepsy (AR) | Maternal | ||
in trans with row 1 | Pyridoxine-dependent epilepsy (AR) | Paternal |
Interpretation
Two ALDH7A1 variants were detected, : c.1279G>C (p.Glu427Gln, maternal) — a — and c.1429G>A (p.Val477Ile, paternal) — a previously unreported variant currently classified as VUS. The patient's phenotype is highly specific for pyridoxine-dependent epilepsy with (elevated α-AASA). The clinical and biochemical evidence strongly supports a PDE-ALDH7A1 diagnosis. The VUS classification of c.1429G>A is ; functional studies of recombinant enzyme activity and/or RNA studies are recommended and would likely upgrade this variant to Likely Pathogenic.
Recommendations
- •Continue pyridoxine supplementation indefinitely; titrate to seizure control and avoid excessive doses (peripheral neuropathy risk).
- •Confirm functional impact of c.1429G>A — either by recombinant enzyme assay or RNA studies. Reclassification to LP would consolidate the molecular diagnosis.
- •Lysine-restricted diet + arginine supplementation may further improve neurodevelopmental outcomes (consult metabolic dietitian).
- •Genetic counseling for the family. Both parents are carriers; 25% recurrence risk per pregnancy.
- •Reclassification of the VUS in 1–2 years per lab policy.