Pyridoxine-dependent epilepsy

What is pyridoxine-dependent epilepsy?

Pyridoxine-dependent epilepsy is a rare form of epilepsy caused by a deficiency of alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) due to a genetic mutation. Pyridoxine is responsible for important reactions in the body, including the breakdown of some chemicals in the brain (also known as neurotransmitters).

When do seizures in PDE start?

Seizures in PDE usually start within a few hours of birth. However, the seizures can also start before birth, while the baby is still in the uterus, in which case the mother will feel a hammering sensation within. The seizures can also develop as late as when the child is two to three years old.

What are the symptoms of PDE?

Multiple types of clinical seizures may be present in children affected by PDE. In addition, recurrent episodes of status epilepticus (i.e. seizures back-to-back without recovery of consciousness or prolonged non-stop seizures) are typically seen.

Apart from uncontrollable seizures, children with PDE may have other symptoms, such as slow development, small head circumference and intellectual disabilities. If untreated, these children can develop global developmental delay.

How is PDE diagnosed?

PDE may be verified by your child’s health-care team by giving your child vitamin B6 orally (by mouth) or intravenously (through a vein) while recording the EEG. After taking 30 mg/kg/day (not exceeding 500 mg/day) of pyridoxine orally, the majority of children with PDE will likely have clinical seizures controlled within five days.

If the seizure stops after vitamin B6 intake and the EEG patterns improve, this indicates that the seizures are pyridoxine-dependent. While intravenous injections of vitamin B6 can reverse seizure activity immediately, it may take several days for the EEG to become normal. A diagnosis of PDE is confirmed with genetic testing.

How is PDE treated?

Seizures in PDE do not typically respond to anti-seizure medications. Instead, your child will need to take vitamin B6, often for their entire life.

If your child is found to have PDE, they will need to take large daily supplements of vitamin B6 every day for many months or years, possibly for the rest of their life. The doctor will discuss this with you.

In addition to vitamin B6 supplementation, a special diet restricted in the amino acid lysine and supplementation of arginine is also recommended to improve developmental outcomes.

What are the side effects of PDE treatment with vitamin B6?

Rarely, children may develop some side effects of vitamin B6, such as nausea, headaches and drowsiness.

When used over the long term, vitamin B6 may cause peripheral neuropathy, a condition in which the nerves that carry information back and forth between the central nervous system and the body are damaged and no longer work properly. This can cause pain, numbness or difficulty controlling the muscles. Your child’s health-care provider will perform regular check-ups including nerve conduction studies to look for and prevent this complication.