Pnpo deficiency - seizures

[Arb26]

My 2 month old has been diagnosed with rare genetic condition of PNPO deficiency at birth following onset of cluster of seizures.

She is currently on PLP therapy.

Any experiences to share with this condition and development prognosis?

Thanks

 

[Bernard]

Hi Arb26, welcome to CWE.

We have a member here @Andrew that has PNPO deficiency and manages his seizures with B vitamins:

Vitamins and Epilepsy

Has anyone had problems taking vitamins? Calcium and magnesium are involved in neuro transmitter function. I think my sodium levels got really low about a week ago (based on previous experience and tests). So, I started taking some vitamins. I'm feeling better, but I'm also more seizure-y...

www.coping-with-epilepsy.com

 

[Andrew]

Hi Arb26,

Just wondering how your daughter is doing regarding PLP therapy.

A

Thread '(((*** 40 years on vitamin b6 ***)))'

Feb 20, 2011

20th February 2011: It was on this day, 40 years ago, that my then paediatrician first administered Pyridoxine HCl (vitamin B6) in the hopes that it would stop my severe seizures.

Here is my story regarding B vitamins:

I had my first seizure at two weeks old. I spent the first six months of my life in and out of hospital. Doctors were mystified by my illness. None of the ‘normal’ antiepileptic drugs that were administered had any positive effects. At this time I was having many ‘different types’ of seizures a day some of which went status. Countless tests were being done including...

• Andrew
• vitamin b6
• Replies: 37
• Forum: The Kitchen

Andrew (PNPO deficient for over 54 years, genetically confirmed in 2012).

 

[Andrew]

I have just noticed a typographical error in my above post sign off. It is over 53 years (54 years on 20th Feb. 2025) since B6 Dependent seizures were found. What am I like! But PNPO Deficiency was genetically confirmed in 2012. Having said that I was born with it.

 

[Andrew]

I asked Copilot "what are the differences between a deficiency in vitamin B6 and a dependency?" and this is the response:

Vitamin B6 deficiency is typically caused by inadequate intake or absorption, while B6 dependency stems from genetic or metabolic impairments that require unusually high levels of B6 for normal function.
Here’s a breakdown of the key differences between the two:

Vitamin B6 Deficiency
• Cause: Usually due to poor diet, malabsorption, certain medications (e.g. isoniazid, penicillamine), alcoholism, or chronic illness.
• Mechanism: Normal metabolic pathways are intact, but B6 levels are too low to support them.
• Symptoms:
• Peripheral neuropathy
• Irritability, depression
• Microcytic anemia
• Seizures (especially in infants)
• Glossitis and cheilitis
• Treatment: Supplementation with standard doses of vitamin B6 (typically 2–50 mg/day) resolves symptoms.

Vitamin B6 Dependency
• Cause: Genetic mutations affecting enzymes that require B6 or convert it into its active form (pyridoxal 5′-phosphate, PLP).
• Mechanism: Even with normal intake, the body cannot properly utilize B6 due to impaired metabolism. Higher-than-normal doses are needed to bypass the defect.
• Symptoms:
• Early-onset seizures unresponsive to standard anticonvulsants
• Intellectual disability
• Anemia
• Developmental delays
• Treatment: Lifelong high-dose B6 therapy (often hundreds of milligrams daily), tailored to the specific enzyme defect.

Clinical Implications
• Deficiency is reversible and often transient.
• Dependency is lifelong and may require genetic diagnosis and personalized dosing.
• In B6-dependent epilepsy (e.g. PNPO deficiency), seizures may only respond to PLP, not pyridoxine, due to conversion defects.

Also:

Vitamin B6 Metabolism and Epilepsy- ILAE Eastern Mediterranean 09 April webinar 2021 04 09​