Pyridoxine-dependent epilepsy (PDE) is a seizure disorder arising from mutations in the ALDH7A1 gene. PDE is a lifelong condition that often accompanies intellectual disability.
The National Institutes of Health (NIH) define PDE as a lifelong seizure disorder that causes status epilepticus. Status epilepticus is when someone experiences prolonged seizures.
PDE can begin to affect a fetus in the womb. Alternatively, symptoms may show after birth or during early infancy.
This article provides a close look at PDE. After detailing who it affects, it discusses its symptoms, causes, and diagnosis. It also details the treatment and outlook for PDE.
According to the NIH, PDE is a rare condition that affects under 5,000 people in the United States. Symptoms are most likely to show before birth or in early infancy.
Because it is so uncommon, researchers cannot reliably estimate whether some populations are at a higher risk of developing this condition. For instance, researchers do not know whether race or ethnicity are risk factors for PDE.
The National Organization for Rare Disorders (NORD) states that PDE affects males and females equally.
Seizures are always present in PDE, as the NIH highlights. People with this condition can also experience status epilepticus, which is a state of prolonged seizure activity. Status epilepticus can cause long-term problems with people’s neurons.
Other symptoms of PDE include:
- atypical movements as a fetus
- delays in the maturation of the brain or nervous system
- breathing problems as a newborn
- a low APGAR score, which is a test that doctors use to evaluate the health of newborn babies
- an underdeveloped corpus callosum, which is the brain area that connects the left and right hemispheres
- feeding difficulties as an infant
Less common symptoms
According to the NORD, PDE arises from mutations in the antiquitin gene ALDH7A1.
Antiquitin is an enzyme that affects the metabolism of several enzymes within the brain. These enzymes function to control the transmission of electrical signals between neurons. They also play an important role in brain development.
There is a strong genetic component to PDE, which follows an autosomal recessive pattern of inheritance. In this inheritance pattern, someone acquires PDE by inheriting a gene characterizing the condition from each biological parent.
If an individual receives only one of these genes alongside a healthy gene, they can carry the disease without any symptoms.
The NORD states that if two parents carrying this gene have a child, the probability that the child will have PDE is 25%. The risk that the child will not have PDE but will carry this condition is 50%.
The likelihood that their child will not receive any of these genes and not carry the condition is 25%.
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Other signs of the condition include seizures that respond to pyridoxine or a high concentration of the enzyme alpha-aminoadipic semialdehyde in the blood or urine.
To be certain that an infant has PDE, doctors need to use molecular genetic testing. This involves taking a sample of their genetic material and testing it in the laboratory. These tests can confirm whether the infant has mutations in the ALDH7A1 gene.
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Because PDE is so rare, researchers have not been able to establish the optimal amounts of B6 supplementation. Guidelines in the above review recommend the following daily dosages:
- newborns: 100 milligrams (mg)
- infants: 30 mg per kilogram (kg) of body weight, with a maximum amount of 300 mg
- children, adolescents, and adults: 30 mg per kg of body weight, with a maximum amount of 500 mg
Doctors may temporarily double these doses if symptoms worsen. This treatment can reduce the severity and frequency of PDE seizures. However, there is no known cure for PDE.
PDE is a lifelong condition with symptoms that can be challenging.
Furthermore, a 2019 paper notes that people with PDE have an increased risk of having intellectual disabilities. A 2022 paper puts this risk at 70%. The risk does not completely disappear, even if treatment is successfully controlling seizures.
People with PDE can live for a long time. However, the above 2022 paper notes that some infants with PDE have died within months, days, or even hours of birth. This can occur due to respiratory distress, a possible symptom of PDE.
PDE is a serious condition that can significantly affect a person’s health and quality of life.
Being a parent or caregiver for someone with this condition can therefore be challenging. However, parents and caregivers can find support at the Epilepsy Foundation.
PDE is a rare seizure disorder that arises due to mutations in the ALDH7A1 gene. If both biological parents have this mutation, there is a 25% risk of their child having PDE.
PDE causes many symptoms, including status epilepticus, which involves an individual having a seizure for minutes at a time. People with PDE are also likely to have significant intellectual disabilities.
Doctors cannot treat PDE with anti-seizure medications, and the condition currently does not have a cure. However, daily supplementation with pyridoxine can alleviate symptoms.