Talk:Pyridoxine-dependent epilepsy

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Ideal sources for Wikipedia's health content are defined in the guideline Wikipedia:Identifying reliable sources (medicine) and are typically review articles. Here are links to possibly useful sources of information about Pyridoxine-dependent epilepsy.

PubMed provides review articles from the past five years (limit to free review articles)
The TRIP database provides clinical publications about evidence-based medicine.
Other potential sources include: Centre for Reviews and Dissemination and CDC

Folinic acid

In a paper titled "a mini-review" (in Molecular Genetics and Metabolism - is it a good secoondary source? The impact factor is 1.3) I found the following:

Some patients who were later proven to have ATQ (antiquitin) deficiency, but had an unclear response to pyridoxine, have shown response to folinic acid. Although the mechanism underlying folinic acid responsiveness in ATQ deficiency has not been elucidated, folinic acid (3–5 mg/kg/day) may have potential benefit as an add-on treatment in neonates, especially in the presence of incomplete pyridoxine responsiveness or of breakthrough seizures. In older patients 10–30 mg/day should be tried [16]. It is unknown whether long-term folinic acid is of benefit once the seizures are stabilized. High dose folinic acid therapy can also exacerbate a seizure disorder, and the clinical benefit has to be closely monitored.

The same paper says that in 1995, an entity titled "folinic acid-responsive seizures" was described, in which kids improved on folinic acid. In 2009, it was shown to the genetically the same as pyridoxine-dependent epilepsy. I think of adding this information in a "History" section.

Further, I found a paper that provides a hypothesis about the action of folinic acid in B6-dependent epilepsy. “The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation.” They write that the SHMT enzyme might be working poorly in the absense of B6, since it depends on it, and this will lead to decreased 5-MTHF. Hence the therapeutic effect from taking folinic acid. But this article is not a secondary source but a description of in-vitro research, and therefore it's maybe not proper to add any mention just yet, until it appears in some review or a book.

Thus, treatment with pyridoxine may restore the normal function of this enzyme and otherwise improve the folate metabolism (decrease oxidative species?), but in some patients, seemingly, it's not enough, and additional folinic acid might help.

The authors of a review on cerebral folate deficiency published in 2019 wrote that they personally found low 5-MHTF levels in the cerebrospinal fluid of two patients with pyridoxine-dependent epilepsy. They list pyridoxine-dependent epilepsy as one of the possible causes of CFD. This may also explain the reaction to folinic acid in some patients, since folinic acid is the drug of choice in cerebral folate deficiency. --CopperKettle (talk) 12:25, 3 June 2022 (UTC)[reply]

On the other hand, treatment with folinic acid is not mentioned in the consensus guidelines published in 2020. --CopperKettle (talk) 16:33, 3 June 2022 (UTC)[reply]