CoPAN

CoPAN, or COASY Protein-Associated Neurodegeneration is caused by a mutation in the COASY gene which codes for a protein named Coenzyme-A Synthase. CoPAN is an NBIA disorder that is characterized by spaticity and weakness of the lower limbs early in the disease and iron accumulation and calcifications found in the globus pallidus.

SYMPTOMS

At this time only a few cases have been identified with this rare form of NBIA. There are only a few cases of CoPAN that have been reported, so information about CoPAN may change once more affected individuals are identified.

At present, the symptoms of CoPAN start to appear in childhood and spasticity and dystonia of the lower limbs are present early on, while dystonia of the mouth and jaw appears later in the disease process. Speech problems are also seen, including stuttering and slurry of words, caused by dysarthria.

Common symptoms

Spastic-dystonic paraparesi develops early in the disease

Oro-mandibular dystonia develops later in the disease

Dysarthria (speech problems)

Axonal neuropathy

Parkinsonism (symptoms similar to Parkinson’s disease)

Cognitive impairment

Obsessive-compulsive behavior

CAUSE

CoPAN is inherited in an autosomal recessive manner. Autosomal” refers to the fact that the COASY gene is located on chromosome 17, which is one of the autosomes (chromosome pairs 1-22). Recessive” refers to the fact that a mutation must be present in both copies of the COASY gene for a person to have CoPAN. If an individual has only one COASY mutation, then they are called a “carrier” for CoPAN. Carriers do not have health problems related to the mutation and often do not know they carry a recessive gene mutation. However, if two CoPAN carriers have a child together, then there is a 25% chance that they will both pass on their recessive COASY gene mutations and have a child with CoPAN. There is a 25% chance of the child having CoPAN and a 50% chance that the child will be a carrier like his/her parents. There is a 25% of the child being no carrier of this mutation.

Carrier testing for at-risk relatives and prenatal testing for pregnancies at risk are suggested if both disease-causing mutations have been identified in an affected family member.

Diagnosis

Diagnosis of CoPAN can be confirmed through genetic testing of the COASY gene to find gene changes. Genetic testing is done through sequence analysis.

CoPan Evaluations

To establish the extent of disease in an individual diagnosed with CoPAN, the following evaluations may be useful:

Management

There is no standard treatment for CoPan and treatments are based on managing symptoms by a team of medical professionals. Individuals with CoPAN are recommended to get the following:

Therapies to manage dystonia

Long-term surveillance for CoPAN

to decrease the impact of CoPAN symptoms and increase quality of life.

While the symptoms of CoPAN typically progress at a slow rate, by the time most reported individuals with CoPAN reach their 30s, they are no longer ambulatory and are confined to a wheelchair.

PROGRESSION

The symptoms of CoPAN typically progress at a slow rate. However, by the time most reported individuals with CoPAN reach their 30s, the majority can no longer walk. The average lifespan varies for individuals with CoPAN, but due to improvements in medical care, more affected individuals are now living into middle age.

Prenatal Testing

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.