Pyridoxine. I still remember when I learned about vitamin B6 deficient epilepsy in medical school. One of the residents quizzed me about the first medication to given to a seizing neonate. I suggested phenobarbital, but he shook his head and said “vitamin B6” – which was something that I had never really heard about before. Technically, pyridoxine is not the first-line treatment in neonatal seizures on most protocols, but vitamin-dependent epilepsies are always on the differential in newborns with seizures. Here are a few things about ALDH7A1 that are new in 2016. Continue reading
The E2 story continues. There has been major progress in identifying the role of de novo mutations in infantile spasms and other epileptic encephalopathies. Over the last two years, more than 20 new genes for epileptic encephalopathies were discovered and we have good evidence suggesting that de novo mutations play a major role in these disorders. Moreover, we have gotten a good sense on how complicated it can be to call a de novo mutation pathogenic given the flood of rare genetic variants in the human genome. However, de novo mutations are not what we think about clinically when assessing a patient with new-onset epileptic encephalopathy. In a clinical setting, we are often concerned about underlying metabolic disorders, many of which are recessive. Accordingly, we felt that the next task of the E2 consortium was to assess the role of inherited variants in epileptic encephalopathies. Just to tell you in advance, it is not as easy as it sounds.
Pyridoxal 5’-phosphate (PLP). PNPO deficiency is a rare neurometabolic disease that presents with severe neonatal epilepsy responsive to pyridoxal phosphate. While the classical clinical presentation is well described, there might be milder versions of this potentially treatable neurometabolic disease that have not been recognized so far. In a recent publication in Brain, the phenotypic spectrum of PNPO deficiency is revisited. In addition to the classical neonatal phenotype, the authors identify patients with later onset and atypical response to pyridoxal phosphate. In addition, they identify a rare, potentially causative PNPO variant that probably gets stuck in most exome filtering pipelines. Continue reading