Mitochondrial-membrane Protein-Associated Neurodegeneration (MPAN) is caused by mutations in the C19orf12 gene. This gene is found on chromosome 19 and is believed to play a role in fatty acid metabolism. It is one of the major forms of NBIA and has distinctive clinical symptoms that differentiate it from other forms of NBIA.
Onset occurs in childhood to early adulthood with spasticity that is more prominent than dystonia, weakness in muscles caused by motor axonal neuropathy, optic atrophy, and neuropsychiatric (mental disorder due to disease of the nervous system) changes.
Most affected individuals are still able to walk as they reach adulthood. Psychiatric signs are common, including impulsive or compulsive behavior, depression and frequent mood changes. Unlike most other forms of NBIA, the vast majority of individuals with MPAN develop progressive cognitive decline.
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An eye exam and an MRI of the brain (T2 –weighted) that shows iron accumulation in the globus pallidus and substantia nigra are keys to diagnosing MPAN.
The most common symptoms are speech and gait difficulties, optic atrophy, generalized dystonia, spasticity and parkinsonism.
Commonly, all age groups experience a decline in cognitive ability that progresses to dementia; prominent neuropsychiatric abnormalities; and movement problems caused by nerve cell abnormalities. Studies reveal a loss of nerve cells, widespread iron deposits, and abnormal axons (a part of nerve cells) called spheroid bodies, in the basal ganglia. Lewy neurites, which are abnormal clusters of protein that develop inside the nerve cells, are present in the globus pallidus, and Lewy bodies and neurites are widespread in other areas of the midbrain and in regions of the globus pallidus called the corpus striatum.
Consider treating with drugs that act on dopamine in the brain. Neuropsychiatric symptoms may require treatment by a psychiatrist.
Medical providers also may seek to manage the disease by performing regular eye exams, as well as neurological tests for dystonia, spasticity and parkinsonism. That may include evaluation of the affected individual’s ability to walk and speak for possible physical, occupational and/or speech therapy.
MPAN is an inherited, autosomal recessive disorder. Because most of our genes exist in pairs (one coming from the mother and one coming from the father), we normally carry two working copies of each gene. When one copy of a recessive gene has a change (mutation) in it, the person should still have normal health. That person is called a carrier. Recessive diseases only occur when both parents are carriers for the same condition and then pass their changed genes on to their child, resulting in two disease-causing mutations.
Statistically, there is a one in four chance that two carriers would have an affected child. The chances are two in four the parents will have a child who is a carrier and one in four that the child will not receive the gene mutation. Carrier testing for at-risk relatives and prenatal testing for pregnancies can be done if both disease-causing mutations have been identified in an affected family member.
If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk can be done. In one test, DNA is extracted from fetal cells obtained by amniocentesis, usually at 15 to 18 weeks’ gestation, and analyzed. Or, sampling is done of the chorionic villus, the tiny finger-like projections on the edge of the placenta, usually at 10 to 12 weeks’ gestation.
Embryo screening, known as preimplantation genetic diagnosis, may be an option for some families in which the disease-causing mutations have been identified.