Dr C P Ravikumar

Pyridoxal 5 Phosphate Dependent Epilepsy
Pyridoxal 5 Phosphate Dependent Epilepsy is a rare genetic metabolic disorder, due to which, babies born with this condition are unable to produce adequate amounts of vitamin B6, causing neonatal onset convulsions, soon after they are born.It is a fairly rare disease, occurring in 1 in every 100,000 to 600,000 individuals. Anti-convulsant medications usually have no effect on these types of seizures. Instead, they respond to supplements of pyridoxine, an active form of vitamin B6.
Pyridoxine dependent epilepsy is an inborn error of metabolism, where mutations in the antiquitin gene /ALDH7A1 gene causes decreased production of enzymes that are required for the assimilation and use of vitamin b6 or pyridoxine and its compounds in the body, without which there are increased chances of neurological conditions like neonatal seizures.  The disease is caused due to autosomal recessive genetic inheritance, which means that the parents of the affected child carry one copy each of the mutated gene. However, the parents do not exhibit signs of the disease themselves.

The disorder is characterized by:
  1. In utero seizures (i.e. the baby experiences convulsions while in the womb)
  2. Fetal distress before delivery
  3. Increased chances of premature birth
  4. Low APGAR score at birth
  5. High pitched cry
  6. Low body temperature (hypothermia)
  7. Poor muscle tone (dystonia)

Typically, the seizures occur 24 hours to 2 weeks after birth. They are:
  1. Tonic – Clonic seizures (characterized by muscle rigidity and loss of consciousness)
  2. Prolonged, intractable convulsions, lasting several minutes (Status Epilepticus)
  3. Resistant to regular anticonvulsant drugs
  4. Causes “Burst Pattern” on EEG  
  5. Respond to treatment with pyridoxine

Atypical features of the disorder are:
  1. Onset that begins later i.e. from infancy to three years
  2. Convulsions that initially respond to antiepileptic drugs and but afterwards become intractable
  3. Seizures during early life that do not respond to pyridoxine but begin to respond to it months later.
  4. Seizure-free intervals , sometimes more than five months, after discontinuation of pyridoxine.  

Long term effects of Neonatal Onset Seizures:
  1. Failure to feed
  2. Failure to thrive
  3. Developmental delays
  4. Learning disabilities

Suspicion of the condition arises with the characteristic features of the convulsions themselves. Confirmation of the disease is usually made by genetic testing and analysis.
The concentration of α-aminoadipic semialdehyde (α-AASA) in urine and plasma  is usually elevated which is a strong indicator of the disorder . Levels of pipecolic acid may also be increased in cerebrospinal fluid and plasma.

Children are given therapeutic doses of pyridoxal 5 phosphate or active forms of vitamin b6 in order to control the convulsions.Long term treatment involves addressing the neurological effects of neonatal onset seizures on the child, like delays in achieving milestones or learning difficulties.

Disclaimer: The above information is for awareness and education purposes only and cannot be used for diagnosis or treatment of any condition. Please consult with a physician for any concerns or questions

Picture of Dr C P Ravikumar

Dr C P Ravikumar

Aster CMI Hospital, Bangalore