This article was published in March of 2023 and reviews the most up-to-date progress in pyridoxine-dependent epilepsy (PDE-ALDH7A1). I’ve included the original article here. CurePDE has broken up the article into smaller sections and adapted it for non-medical readers looking for a concise introduction to the topic using plain scientific language.
If you would like to read the introduction, please go here.
If you would like to read about the three forms of PDE go here.
Natural History
PDE-ALDH7A1 is a rare type of epileptic encephalopathy that is inherited in a way where both parents need to pass on a specific gene. It’s not very common, and about 1 in 64,352 births may have this condition. Over 200 people with PDE-ALDH7A1 have been reported, and it usually shows up in newborns. These babies often have seizures that don’t respond to regular medications, and sometimes, their mothers notice unusual movements before birth. Some babies might seem like they had trouble breathing at birth, which can make it hard to diagnose PDE-ALDH7A1 right away. The seizures can be different, like partial, generalized, atonic, myoclonic events, and spasms. In many cases, patients have ongoing seizures, even if it’s not always obvious.
The way PDE-ALDH7A1 affects people can vary. Usually, adding a vitamin called pyridoxine helps control seizures, but some patients may still need other seizure medications over time. About 75% of patients have some kind of developmental issues, from mild to severe, like problems with thinking, autism traits, and behavior challenges. Talking skills, especially expressing themselves, can be harder. People who get seizures later or are diagnosed and treated early tend to have a better outlook, but it’s not always the case. The differences in how the condition progresses may be because of brain issues, not understanding the link between genes and how it shows up, and the levels of certain substances in the body.
Associated Developmental Features
People with PDE-ALDH7A1 might have issues with how their brains develop, which can be there from birth or get worse over time. One common problem is the thinning of a part of the brain called the posterior corpus callosum, especially the isthmus, which can be seen on special pictures called magnetic resonance imaging (MRI). About 20% of patients also have other abnormalities in the back part of the brain, like a large space called mega cisterna magna. Sometimes, unusual brain structures like heterotopia and problems with how the cortex forms are found in imaging and studies looking at the brain’s tissue.
In rare cases, patients may have problems like obstructive hydrocephalus (fluid buildup in the brain) and the brain’s ventricles getting bigger over time (hydrocephalus ex vacuo). This might happen when the diagnosis is made late or seizures are not well controlled. Other things that can be different in people with PDE-ALDH7A1 include congenital cataracts (eye issues present from birth) and a variety of facial features like wide-set eyes, a flat nose bridge, folds in the corners of the eyes, a high hairline, a pointed chin, full eyebrows, and a broad nose base.
