(Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration) is a rare disorder that is characterized by a progressive childhood-onset movement disorder and optic atrophy. Although MEPAN does not appear to involve brain iron accumulation, both the symptoms and the brain regions involved overlap with NBIA. For these reasons, nbiacure team was involved in the gene discovery and continues to have an interest in this NBIA “mimic.”
MEPAN is more frequent in individuals of Ashkenazi Jewish ancestry. However, it has also been described in individuals of other ethnicities.
The movement disorder symptoms of MEPAN usually start to appear during childhood before age 7. Over time some individuals require a walker or wheelchair for ambulation; others may never learn to walk
Decreased vision typically begins in childhood and can lead to blindness in adulthood.
Currently only 13 individuals known to have MEPAN, therefore the full spectrum of symptoms and progression have not been defined yet.
Dysarthria (poor articulation or slurring of speech) Progressive speech problems. it can make difficult to be understood by acquaintances and others in the community. Usually people close to the individuals with MEPAN have learned to better understand their speech.
Involuntary movements, Typically start to develop between 15 months – 6.5 years of age.
- Dystonia (involuntary muscle contraction and spasms) is the most common symptom.
- Chorea and/or ataxia may also occur.
- Optic atrophy (deterioration of the nerve that connects the eye to the brain). Manifest as reduced visual acuity in childhood. Can lead to functional blindness in adulthood in some individuals.
- Nystagmus (roving eye movements) can also be seen
Cognition Intellect is often (but not always) preserved
Hyperintesity T2 signal (bright patches) Bilateral in one or more structures of the basal ganglia (i.e., caudate, putamen or pallidum) evident around the onset of dystonia.
Genetic testing diagnosis of MEPAN is confirmed if two changes in MECR gene is confirmed.
If no gene change or only one gene change is found through sequence analysis of the MECR gene, then deletion/duplication analysis could be considered. However, to date no exonic or whole gene deletions have been reported.
Since MEPAN is still a relatively new and rare diagnosis, it is likely that testing may change over time and that the symptoms of MEPAN will become better understood and potentially more recognizable in the coming years.
There is no standard treatment for MEPAN. A team of medical professionals recommends treatments based on current symptoms.
Evaluations to determine the extent of the disease:
- Ophthalmology evaluation to assess for optic atrophy and visual acuity
- Neurological examination for dystonia
- Neuropsychological examination to assess cognitive function
- Assessment for physical therapy, occupational therapy, and/or speech therapy
- Medical genetics consultation
Therapies and medications
- Visual aids can be used in cases of decreased visual acuity
- Physiotherapy can be used to maintain range of movement
- Special aids such as braces, walkers and wheelchairs can maintain/improve mobility
- Speech therapy, if speech dysarthria is present, and assessment for augmentative communication devices
Anticholinergic agents, baclofen and benzodiazepines may relieve dystonia,
- Anticholinergic agents act peripherally on the on the neuromuscular junction, but can have a variety of adverse central nervous system (CNS) effects.
- Baclofen, which works on GABAB receptors and functions as a CNS depressant and skeletal muscle relaxant, can be administered either through a spinal pump or systemically. Benzodiazepines which are GABAA agonists, can reduce muscle tone and alleviate the dystonia; however, they also cause sedation.
While some patients with severe dystonia are treated with DBS, experience with MEPAN is limited and, to date, there are no reports of individuals with this disorder treated with DBS. Moreover, due to the existence of basal ganglia lesions, DBS may not be suitable for many individuals with MEPAN
- Yearly eye exams
- Yearly neurological assessment to determine need for additional interventions, including speech therapy
It is unknown what kind of impact MEPAN has on life expectancy. Two of the oldest are in their 40s and 50s.
The altered MECR gene inherited in an autosomal recessive manner is the cause of MEPAN. “Autosomal” refers to the fact that the MECR gene is located on chromosome 1, which is one of the autosomes (chromosome pairs 1-22). “Recessive” refers to the fact that a gene change must be present in both copies of the MECR gene for a person to have MEPAN.
MECR is the only gene known to cause MEPAN. The MECR encodes à protein called mitochondrial trans-2-enoyl-coenzyme A-reductase, un enzyme, that is necessary for the last step in mitochondrial fatty acid synthesis, which turns trans-2-enoyl-acyl carrier protein into acyl-ACP. MECR also serves as the precursor for lipoic acid synthesis which functions as a cofactor for key enzymes of the respiratory chain. Therefore, decreased MECR activity reduces mitochondrial RNA processing and translation, as well as respiratory complex assembly.
If an individual has only one MECR gene change, then they are called a “carrier” for MEPAN. Carriers do not have health problems related to that gene change and often do not know they carry a recessive gene change. However, if two MEPAN carriers have a child together, then there is a 25% chance to have a child with MEPAN, a 50% chance that the child will be a carrier like his/her parents and a 25% chance that the child will not have MEPAN or be a carrier.
For more info: www.nbiacure.org, https://www.mepan.org