What Is MEPAN Syndrome?
It is an acronym for Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration. It is a progressive genetic disorder with a childhood onset affecting movement and vision. The symptoms seen in neurodegeneration with brain iron accumulation (NBIA) are similar to MEPAN syndrome because the affected areas of the brain that cause NBIA and MEPAN syndrome, but the latter does not have any brain iron accumulation.
What Are the Symptoms of MEPAN Syndrome?
The symptoms related to movement and vision start to appear before the age of seven, gradually progressing to complete immobility and blindness as the patient reaches adulthood. Below are some of the other symptoms of MEPAN syndrome-
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Dysarthria- Speech problems due to poor articulation and pronunciation. The patient's speech can only be understood by people who are close to them and have learned to comprehend it.
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Dystonia- This is a movement disorder that causes the muscles to contract involuntarily, resulting in repetitive and twisting movements, usually starting between 15 months to 6.5 years in MEPAN patients.
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Chorea- This is also a movement disorder like dystonia, but the movements in chorea are fidgety and dance-like, appearing in the hands, feet, and face. They appear as if the patient is dancing or playing the piano.
Other signs of chorea are the milkmaid's grip and the jack-in-the-box-tongue. As the name suggests, the patient's hand movements will resemble the grip of a milkmaid while milking a cow, and when the patient tries to stick out their tongue, it will slide in and out, similar to a jack-in-the-box.
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Ataxia - It is the term used for a group of disorders that affect coordination and balance; MEPAN patients will eventually need a walker or wheelchair for ambulation.
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Optic Atrophy - It is a condition where the optic nerve shrinks due to degeneration of retinal ganglion cells (RGC) axons. It manifests at an early age in MEPAN patients as reduced visual acuity.
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Nystagmus - This is the repetitive and uncontrolled movements of the eye, a feature which is in theme with the poor muscle control character of MEPAN patients.
In spite of the gradual motor impairment, patients with MEPAN syndrome have intact cognition; they will be able to process the acquired knowledge and understand through thought, experience, and senses.
What Causes MEPAN Syndrome?
MEPAN syndrome is caused by mutations in the MECR gene. MECR is a gene responsible for the completion of mitochondrial fatty acid synthesis and is a precursor for lipoic acid synthesis. A mutation (alteration) in this gene will reduce the synthesis of mitochondrial fatty acids and lipoic acid. This will lead to neurological complications related to movement and vision.
MEPAN syndrome is transmitted through autosomal recessive inheritance. An autosome is any chromosome that is not a sex chromosome, and an autosomal inheritance means the gene responsible for the function (in normal individuals) and condition (in affected individuals) is present on one of the autosomes.
Gender has nothing to do with autosomal inheritance. Humans receive half of the chromosomes from the mother (11 pairs + X) and the other half from the father (11 pairs + X/Y). The term recessive means for the individual to be affected, they should receive the MECR mutation from both the parents. The chances of this happening (assuming both the parents are carriers of the condition) are 25 %.
How Is MEPAN Syndrome Diagnosed?
The only way to confirm MEPAN is through genetic testing of the MECR gene, but at times the MECR gene analysis will result in no gene change or only one gene change indicating negative for MECR mutation. To avoid misdiagnosis in these situations, the clinician will request an MRI (magnetic resonance imaging).
An MRI uses a magnetic field and a computer to produce a picture of the body; it is less invasive and safe and can even be used in pregnant patients. In MEPAN patients, an MRI will detect bilateral hyperintense T2 signal from the basal ganglia, indicative of the onset of dystonia.
Along with the imaging, the clinician will also recommend a few evaluations to determine the extent of the condition; they are-
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Ophthalmology evaluation to check optic atrophy and visual acuity.
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Neurological exam to evaluate dystonia.
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Neuropsychological exam to evaluate cognitive function.
Once the symptoms are identified, further assessment will be done to assess the patient for physical therapy, occupational therapy, and speech therapy.
What Is the Treatment for MEPAN Syndrome?
Unlike other genetic conditions, replacement gene therapy has not been a treatment option for this autosomal recessive disorder because the natural history of disease progression and other aspects of this syndrome has not yet been completely defined.
As of now, treatment involves-
A. Management of Symptoms- This includes-
1. Visual aids to improve visual acuity.
2. Physiotherapy to improve movement range.
3. Skills required for daily activity can be developed and maintained with the help of occupational therapy.
4. Mobility can be improved with the help of braces, walkers, and wheelchairs.
5. Augmentative communication devices can be used in patients with dysarthria.
6. Dystonia can be relieved with the help of medication; some of them are-
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Anticholinergic Agents - They act on the neuromuscular junction by binding to the acetylcholinesterase and inhibiting its action.
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Baclofen - It functions as a central nervous system depressant and skeletal muscle relaxant.
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Benzodiazepines - They reduce muscle tone and minimize dystonia.
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Other symptomatic treatments to alleviate dystonia include deep brain stimulation (DBS) and ADHD (attention deficit hyper disorder) medication. They have been helpful in a few patients, but their long-term efficacy is yet to be determined.
B. Surveillance - This includes yearly eye and neurological examinations to determine the need for visual aids and additional interventions.
Circumstances to Avoid - Stress and febrile illness exacerbate the symptoms; therefore, precautions should be taken to prevent or avoid them.
Therapies Under Investigation - Nutritional supplementation therapy is currently under investigation; this includes supplementing the patient with lipoic acid (LA), octanoic acid (C8), and mito cocktail (containing riboflavin, thiamine, coenzyme Q10, and alpha-lipoic acid), vitamin E and vitamin C.
Conclusion:
MEPAN syndrome is a genetic disorder that causes gradual loss of movement, vision, and other motor functions in the affected individual. There have been only 13 reported cases of MEPAN so far, and the information available from these cases is being used for diagnosis and symptomatic management. Awareness about the condition will help to gather more information, and it can be done with the help of technology and genetic counseling.
