Pyridoxine dependency
Epilepsy Action is indebted to Dr Richard Appleton, a Consultant Paediatric Neurologist who specialises in children’s epilepsy, and to Dr Rachel Kneen, Consultant Paediatric Neurologist and Dr Stewart Macleod, Specialist Registrar in paediatric neurology, at Alder Hey Children’s Hospital, Liverpool, who have kindly prepared the information on this page.
Pyridoxine
Pyridoxine (also called vitamin B6, which is one of the 
B-complex vitamins) dependency is a very rare condition that has been recognised for about 50 years. The condition is also sometimes called pyridoxine responsive epilepsy.
Although it is not exactly known how rare the condition really is, it probably occurs in no more than 1 in 200,000-400,000 children. The condition usually presents in the first few days or weeks of life but may present in the week or two before the baby is born (called in-utero seizures) or as late as 15 or 18 months of age.
The seizures may be all types - myoclonic, clonic, tonic, tonic-clonic or even infantile spasms. It is in fact quite common for an infant with pyridoxine-dependency to have many different types of seizures, all at the same time.
No specific tests
Occasionally young children who present with infantile spasms in the first year of life (and these children have a type of epilepsy called West Syndrome) will respond to pyridoxine but this does not always mean that they will have pyridoxine-dependency. In view of this, a number of doctors - particularly in Japan and some Eastern European countries - will give pyridoxine as the very first drug when an infant presents with infantile spasms, in case they may have pyridoxine-dependency. However, less than 10 per cent of children who present with infantile spasms as their first or only seizure type actually turn out to have genuine pyridoxine-dependency. Clearly this means that at least 90 per cent of children with infantile spasms do not have pyridoxine-dependency.
There are no specific tests that can diagnose pyridoxine-dependency including blood and urine tests or brain scans (either a computerised tomography (CT), or magnetic resonance imaging (MRI) scan). The electroencephalogram (EEG) is usually very abnormal in children with pyridoxine-dependency and may even look like the EEG pattern in infants who have West Syndrome who have infantile spasms and which is called hypsarrhythmia. The diagnosis of pyridoxine-dependency is usually based on what is called a drug trial, or ‘therapeutic challenge’.
A therapeutic challenge
This means the following: When a child is thought to have the condition, pyridoxine (vitamin B6) is given for a period of time, varying from a few days, or ideally, for three or four weeks.
If the child’s seizures continue after a three or four week trial of pyridoxine, then it is very unlikely that they have pyridoxine-dependency.
If the child’s seizures show a dramatic reduction or cease altogether, then the pyridoxine is stopped immediately (not withdrawn gradually first). If the child’s seizures then recur, the pyridoxine is restarted. If the seizures then stop again after the pyridoxine has been restarted, then this makes the diagnosis of pyridoxine-dependency very likely.
The pyridoxine is then continued, either indefinitely or certainly for the next 12 months before deciding whether to undertake another ‘therapeutic challenge’ by stopping the drug.
Pyridoxine is given by mouth, usually twice a day. Sometimes the drug may be injected into a vein while the child is having an EEG to see if the EEG becomes normal during or immediately after the injection. Clearly this must only be carried out in specialist centres. It is also important to understand that even if the EEG remains abnormal during or just after the injection of pyridoxine, this does not necessarily exclude a diagnosis of pyridoxine-dependency. For this reason most specialists (paediatric neurologists) would recommend giving pyridoxine by mouth for at least three or four weeks.
The dose of pyridoxine is based on the child’s weight; some children need only a small dose, while others need quite high doses, depending on how quickly the seizures stop after pyridoxine is prescribed. Pyridoxine is given either once or twice a day. When given by mouth, pyridoxine has very few long-term side effects.
A very rare condition
Most, if not all children who have pyridoxine-dependency do not respond to the commonly used antiepileptic drugs (also called anticonvulsants), such as carbamazepine, sodium valproate, lamotrigine, topiramate, phenobarbitone, phenytoin or diazepam. In view of this and the fact that, once diagnosed, pyridoxine-dependency is so easily treated, most specialists would always consider giving a three or four week course (a ‘therapeutic trial’) of pyridoxine to all children who present with epileptic seizures in the first year of life and where the seizures do not respond to the usual antiepileptic drugs. However, it is again important to emphasise that despite this approach pyridoxine-dependency remains a very rare condition, and a very rare cause of epilepsy in children. In 11 years at Alder Hey I have often thought about the diagnosis and given a trial of pyridoxine but have never actually found or diagnosed a child with pyridoxine-dependency!
Possible causes
It is not entirely clear why pyridoxine-dependency causes epilepsy. However the most likely explanation is that pyridoxine is used by the body to make a substance within the brain called gamma aminobutyric acid (GABA). GABA is one of a group of chemicals found within the brain called neurotransmitters which are very important in epilepsy.
The other most important neurotransmitter in the brain is one called glutamic acid, which is an excitatory neurotransmitter. GABA is an inhibitory neurotransmitter - which means that it has a crucial function in inhibiting or preventing epileptic seizures. If pyridoxine is not being used properly (as occurs in pyridoxine-dependency), then GABA will not be present in sufficient amounts and therefore seizures will not be prevented, and are likely to occur very frequently.
The inheritance factor
Pyridoxine-dependency is a genetic disorder - which means that it is inherited. The pattern of inheritance is what is called ‘autosomal recessive’, which means that both parents are carriers of the disorder but do not have the disorder themselves. At the current time the gene or genes that may be responsible for pyridoxine-dependency have not been found and therefore there is no test to find out who may be carriers.
Epilepsy Helpline
- UK freephone 0808 800 5050
- International +44 113 210 8850
- Email: helpline@epilepsy.org.uk
- Txt msg: 07797 805 390 info
Twitter Updates
Epilepsy Action blog
Comments
My son is now 9 years old and has been diagnosed with this condition for almost a year. He had seizures from birth and after many different trials of anti-convulsants, Pyridoxine was given as a precaution alongside other vitamins. We only new for certain last year when after 4 years of being siezure free our consultant wanted to check the levels of Pyridoxine in my sons blood. We took him off the medicine immediatly and within 3 days he had a seizure.
We are so glad to finally know what is the cause and to be able to give it a name. We are currently taking part in investigations that could help to identify Pyridoxine Dependency and the gene that causes it in the future.
Although this means we are both carriers of a rare defective gene that could affect our childrens children I feel that fore-warned is fore-armed and am now at long last able to look to the future.
Our son is doing great and is a happy, loving little boy who goes to a great special needs school and with the help of Pyridoxine tablets and the great doctors that are there for him he has a great future ahead of him.
If you would like a parents percpective of the condition please do not hesitate to contact me.
With Love
x
My 3 year old daughter was diagnosed with PDS at 10 weeks of age. She has been seizure free ever since until a recent episode which her b-6 dose was increased to 400 mg/day. There is testing at Seattle Children's Hospital in Washington State which identifies the mutation. My daughter was tested recently and my 8 month old son was tested immediately after birth. He was shown to be a carrier. Dr. Sidney Gospe at Seattle Children's is conducting research on PDS. You can find him on the internet by conductinga search of his name.
Hope that is helpful. Please contact me with any questions.
Hi my daughter is pyridoxine dependent I know is very rare but could you tell me how my
Children in the uk have this rare condition, my daughter is nearly three now and her seizures
Started on day three of birth and took a year to be diagnosed now she off all the other
Anti convulsion meds and is soley on pyridoxine, she was delayed a bit but has now caught
And is doing great its a mirical to see her like this now, my daughter was also born
With a catarax in her right eye is this related, I would love to hear from you and also help
You in answering any questions you may have about this condition.
Many thanks
Shakila azam
Thank you for allowing me to ask you a couple of questions. Seizures are a terror to any child and family. I'm relieved to hear that your child is thriving. I would love your help...
I have some questions from a parental point of view. My son has seizures that were disregarded as a hyper reflex in the first 24 hours of his life. I had hammering sensations in utero at about 8 months. The reflex for the first 2 months of his life were disregarded as something he would outgrow. At 3 months, febrile, he had a focal seizure that involved the whole left side of his body. Since then, he's had numerous seizures all different types, status epilepticus on many occasions and involving either side. My son is now 2 years old and we are on a B6 trial of 150 mg per day. He's gone from having 100's of tiny myoclonics to 1 convulsive seizure every 2 weeks when febrile or associated with illness. He's been on B6 since November.
Our neurologist is skeptical that he has a B6 dependency because it's so rare and he's never seen a patient with it and therefore has given us no guidance as to whether we can increase the dose to see if we see any further results. The doctor thinks he has Dravet Syndrome, but we do not have a confirmation yet of SCN1A genetic test results.
Does this sound like we are on a fair trial? Does a 2 year old at 25 pounds require more than 150 mg per day? I once gave him his daily dose 12 hours later than usual and noticed he was having very unusual seizures. Could this have been a withdrawal from not receiving his dose?
Would really appreciate some guidance. At the moment, he is not quite walking and speaking rather unclearly, but I truly believe he could if he wasn't on triple the dose of Valproate and maximum doses of both Clobazam and Keppra.
Any insight would be great,
Celestine
Our daughter was born in February 2007 and within 20 minutes of birth she started twitching in the face, we notified the doctors and they took her down to Neo-natal they told us there is no problem it is the trauma of birth, as she was delivered by forceps.
By the following morning she started having full blown seizures these lasted for a total of 14 days. She was placed on every Anti Convulsion drug you can think of and sometimes on the biggest dose she could have. By day 11 we were out of our minds we felt they were just leaving her she was sedated most of the time, we even asked nurses could she be moved to Alder Hey in Liverpool but fortunate for us a new doctor from Alder Hey came to work in the hospital his first patient was our daughter he looked at her records and said we should try a drug called pyridoxine but as the condition is very rare and the drug is expensive they would have to order it and it would take 36 hours to be received at the hospital, he did warn us that he had only seen 1 confirmed case of the condition in 12 years and that was in India he told us don’t get your hopes up it probably will not work.
Our daughter was 14 days old and we were woken by nurses telling us she was in her worst seizures yet, it was scary and worrying. Within the next 10 minutes the Pyridoxine arrived at the hospital. They injected her with the loading dose and within 30 seconds she stopped fitting, the nurses cried with relief but the doctors did not believe this was her condition as she was loaded up on Anti Convulsion drugs, as the days passed she started to come of the other drugs and each day she started to get better, 14 days later she was discharged from hospital on 0.83ml of pyridoxine a day (300mg/5ml).
At 3 months old she went for a MRI Scan and a EEG and there was no sign of any brain damage of which we are extremely grateful, as there is no confirmed tests for Pyridoxine Dependency doctors wanted to take our daughter of the pyridoxine to do a trial they wanted to allow her to re-fit and then give her another loading dose and if she stopped fitting that was a confirmed case. We as parents refused this as she had fitting for 24 hours a day for 14 days and no damage 1 more fit may have cause damage.
She then went back into hospital for a Lumbar puncture, blood sample and urine sample at 4 months old this was then to be sent away to the University of Sheffield a professor was to then try and devise a test, We were called to the hospital in December 2007 and it was confirmed case of the condition Pyridoxine Dependent Epilepsy.
She had a further MRI scan in April 2009 and they confirmed again there was no abnormality.
Our daughter has had delays in crawling and walking and now has a severe speech delay which we are working on at the minute.
One of our Daughter’s consultants is the person who wrote this article and we would be grateful that article is changed that she has met and now knows a child in the UK which has been diagnosed with this condition.
We are lucky our daughter goes to a normal main stream nursery and she has fantastic people working with her day in day out.
Her current dose is 1.5 ml once a day (300mg/5ml)
Hope this helps never give up if your child is having seizures ask for this drug what have you to lose I want to fight for every child who is born having convulsions to have a loading dose of Pyridoxine it is a vitamin (B6) it will not harm your child not like anti convulsion drugs can, just because the likes of phenytoin are cheaper drugs, at the end of the day it does not matter about how much Pyridoxine costs, it must cost more to keep a baby in neo-natal for a month.
Here Here !!! Well said !!!
Dear Shakila,
I am sorry to hear your daughter has the condition but like many she seems to be doing okay which is good news.
I'm not sure if you've been told but Pyridoxine Dependency is caused by genes that the parents carry ( I am not a doctor so if my wording is wrong I apologise). We have a 1 in 4 chance of another child of ours getting it as we are both carriers. My 12year old son is not Pyridoxine Dependent but will have the option to have a test done when he is older to see if he is a carrier.
We did not know we were affected and are otherwise fit and healthy. We both have large families and so far none of our siblings have had children that are affected by it.
There are people all over the world with this rare disease and we can't blame ourselves or anyone else for not knowing if we are a carrier. It could happen to anyone. We all feel guilty and would gladly take the place of our children and take their suffering away but perhaps it makes them stronger people in the long run.
As for your daughters cattarachs I am not sure if PDS can have caused this, you should speak to your Consultant or optician.
I wish you and your daughter well in the future.
Vicki x