Mitchell Syndrome
Mitchell Syndrome is a rare genetic disorder characterised by neurological problems that affect children and individuals of all ages. Due to its rarity and varying presentation, the syndrome remained unidentified throughout human history until recent advancements in genetic sequencing. As of June 2022, only 15 individuals have been diagnosed with Mitchell Syndrome, including children, teenagers, and adults, with Mitchell Herndon being most well known for having this mutation.
Genetic Mutation and Peroxisomal Dysfunction
Mitchell Syndrome results from a specific genetic mutation on the ACOX1 gene found in the individual's DNA. This mutation is not typically inherited from parents but rather occurs spontaneously during the embryonic stage of a child's development. The mutation disrupts the normal functioning of peroxisomes, which are small structures within our cells responsible for breaking down fatty acids into energy and essential materials for cell function.
In individuals with Mitchell Syndrome, the ACOX1 mutation causes peroxisomes to metabolise these fatty acids too quickly, leading to an excessive production of hydrogen peroxide as a by-product. While cells can usually eliminate hydrogen peroxide, individuals with Mitchell Syndrome face difficulties in this process. Accumulation of hydrogen peroxide within the cells becomes toxic, gradually damaging and destroying the cells affected by the syndrome.
Impact on Schwann Cells and Nervous System
Mitchell Syndrome primarily affects a specific type of cell called Schwann cells, which play a crucial role in forming the protective myelin sheath around nerves. The myelin sheath facilitates the transmission of signals between the brain and the body. The build-up of hydrogen peroxide resulting from the ACOX1 mutation is particularly destructive to Schwann cells, leading to damage to the myelin sheathing and subsequent impairment of axons—the nerve fibres responsible for transmitting signals.
The damage to axons in individuals with Mitchell Syndrome manifests as mobility and balance problems, along with the gradual loss of gross and fine motor skills. Additionally, common symptoms may include hearing impairments, vision problems, skin issues, and, in some cases, cognitive decline as the disease progresses.
Variability in Presentation and Related Disorders
Mitchell Syndrome exhibits variations in its presentation among different individuals. The age of onset, type, and severity of symptoms can differ significantly, and the underlying reasons for this variability are not yet fully understood. It is worth noting that Mitchell Syndrome is related to other peroxisomal disorders, such as ACOX1 deficiency. While both conditions involve mutations on the ACOX1 gene, they are distinct diseases with their own unique symptoms and clinical presentations.
Current Treatments and Research
As of now, there is no specific cure for Mitchell Syndrome. However, there are potential treatment avenues that offer hope for individuals affected by the condition. Gene therapies show promise in addressing the underlying genetic mutation associated with Mitchell Syndrome, although these treatments are still in the developmental stages and not widely available.
Additionally, a potential treatment approach involves the use of an antioxidant called N-acetylcysteine amide (NACA), which may help mitigate the damaging effects of hydrogen peroxide on Schwann cells. However, it is important to note that NACA is an experimental medication, not yet tested for its efficacy in Mitchell Syndrome, and not currently accessible for individuals with the condition.
