There have been several theories proposed in the past.
Firstly, some believed that there might be a problem with the neurotransmitters (chemical substances responsible for signaling between nerve cells) in the brain, as this would explain why all of the brain could be affected. However treatments such as bromides (which are thought to act via neurotransmitters) have not been effective in all patients and measurement of neurotransmitter levels done in some of the previously reported cases have been normal.
Another possibility was a problem with the channels in the cell membrane which regulate the flow of sodium and potassium in and out of cells. Mutations in these genes, causing conditions known as channelopathies, have in recent years been found to be the cause of several different epilepsy syndromes such as Dravet syndrome also known as severe myoclonic epilepsy of infancy (SMEI).
Other possibilities that have been considered include metabolic conditions including mitochondrial diseases - however most previously reported cases of MPSI have been extensively investigated including blood, urine, cerebrospinal fluid testing and muscle biopsy and no biochemical abnormalities have been found.
It is believed that some cases of MPSI have an inherited basis. Most likely, a faulty gene might have been passed down from each parent, resulting in an affected child.
It is also possible that the occurrence might be spontaneous i.e. might have just occurred by chance in the child affected. This has been considerd as there are limited reports of affected siblings.
Recent research undetaken by Dr Amy Mctague et al (Brain 2013) has identified faulty genes in a number of affected children, which are believed to be the cause of their MPSI. Further work is currently being undertaken to see whether these mutations were inherited from the parents or happened spontaneously and only in that child.
Research evidence indicates that there is more than one genetic abnormality that can cause MPSI. This also explains the varying symptoms between affected children and why for some the onset is severe with death often occurring in the first few years of life whilst others have a more gradual onset, with less additional complications.