Update on the treatment of vitamin B6 dependent epilepsies

ABSTRACT

Introduction: Vitamin B6 dependent epilepsies are a group of treatable diseases (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinaemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects) responding to pyridoxine or pyridoxal-5^I-phosphate.

Areas covered: A critical review was conducted on the therapeutic management of all the reported patients with genetically confirmed diagnoses of diseases affecting vitamin B6 metabolism and presenting with pyridoxine or pyridoxal-5^I-phosphate dependent-seizures. Data about safety and efficacy were analyzed as well as the management of supplementation with pyridoxine or pyridoxal-5^I-phosphate both in the acute phases and in the maintenance therapies. The authors also analyzed alternative therapeutic strategies for ALDH7A1 deficiency (lysine-restricted diet, arginine supplementation, oligonucleotide antisense therapy, upstream inhibition of aminoadipic semialdehyde synthase).

Expert opinion: The administration of pyridoxine or pyridoxal-5^I-phosphate should be considered in all intractable seizures also beyond the first year of life. Lysine restricted diet and arginine supplementation should be introduced in all the confirmed ALDH7A1 deficient patients. Pre or post-natal supplementation with pyridoxine should be given in familial cases until an eventual molecular genetic disconfirmation. Minor data about alternative therapies are available for other disorders of vitamin B6 metabolism.

KEYWORDS:

• Metabolic epilepsies
• pyridoxine
• pyridoxal-5^I-phospate
• epileptic encephalopathies
• children

Article highlights

• Pyridoxine or PLP trials should be performed in all newborns/infants with intractable seizures.

• Recent evidences support the possible indication of these trials also in children older than 12–24 months with a negative response to other antiepileptic treatments.

• Recommended dosages are 100 mg/Kg intravenously or 30 mg/Kg/day orally for pyridoxine and 50–100 /mg/Kg/day orally for PLP in the acute phases and 15–30 mg/Kg/day for pyridoxine and 30–60 mg/Kg/day for PLP as maintenance treatments.

• Supplementation with pyridoxine or PLP should be continued in all responsive patients until an eventual molecular genetic disconfirmation of the diagnosis.

• Prophylactic B6 supplementations should be considered in families at risk with previous confirmed cases.

• Lysine restricted diet and arginine supplementation should be added to vitamin B6 supplementation after having confirmed the diagnosis.

• Future therapeutic strategies include the implementation in clinical trials of oligonucleotide antisense therapy and upstream inhibition of aminoadipic semialdehyde synthase.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.