What neuronal membranes are made of – CERS1 in progressive myoclonus epilepsy

Ceramide. Sphingolipids are a major component of neuronal membranes and help neurons in intracellular signaling and trafficking. Ceramide is one of the basic building blocks of sphingolipids. In a recent publication in Annals of Neurology, mutations in CERS1, coding for ceramide synthetase, are identified in a family with progressive myoclonus epilepsy – and provides an unexpected linked between a group of storage disorders such as Niemann-Pick disease and Tay-Sachs disease and progressive myoclonus epilepsies. Continue reading

Treatable causes of intellectual disability and epilepsy that you don’t want to miss

Think metabolic. We have discussed de novo mutations as a cause of epileptic encephalopathies repeatedly on our blog. While there is emerging evidence that de novo mutations in established genes such as SCN1A or CDKL5 or novel genes including GNAO1 or CHD2 are a major cause of genetic morbidity in patients with epileptic encephalopathies, investigations for de novo mutations are not the immediate knee-jerk reaction in clinical practice. In fact, if a child presents with an epileptic encephalopathy, excluding inborn errors of metabolism (IEM) takes priority. While metabolic causes of epileptic encephalopathies are rare, they need to be excluded as some of these conditions are treatable. In a recent review in Molecular Genetics and Metabolism, van Karnebeek and colleagues review the 89 causes of intellectual disability that are potentially treatable. Many of these conditions also present with epilepsy. They present an updated diagnostic algorithm and provide an online resource for these conditions – in a nutshell, there is an app for that.  Continue reading

How to become a pediatric neurologist

Milestones. Today I passed my board exam for pediatric neurology or neuropediatrics, as we call it in Germany. Even though I am usually not big on celebrating occasions like this, I wanted to use this blog post to reflect upon a journey that led me to three different continents and started eleven years ago in the foothills of AppalachiaContinue reading

GOSR2, North Sea myoclonus and the Haithabu variant

Wall Street. Between the 8th and 11th century, Haithabu (Hebedy), a Viking town in Northern Germany close to the border to Denmark was the Manhattan of its time – a flourishing trading town located at a busy shipping route at a natural short passage connecting the Eider and the Treene river, a precursor of the modern-day Kiel canal. The  Vikings used this shortcut to avoid the dangerous Skagerak when heading West on their conquests. When subsequently settling down in many regions of the North Sea coast, they carried their genetic heritage with them, including a rare variant in the GOSR2 gene, which results in a devastating epilepsy when homozygous. A recent paper in Brain now delineates the phenotype of the “North Sea” progressive myoclonus epilepsy. Continue reading