CoPAN
COASY Protein-Associated Neurodegeneration is caused by a mutation in the COASY gene. At this time only a few cases have been identified with this rare form of NBIA. At present, it appears that onset usually occurs 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.
Clinical Diagnosis
T2-weighted MRI views of the brain with findings showing hypointensity in the substantia nigra and the globus pallidus were found in one case, as well as hyperintensity and swelling in the caudate nuclei, putamina and thalamus in another individual. There was also reported calcifications in the globus pallidus in one individual.
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 Following Initial Diagnosis
To establish the extent of disease in an individual diagnosed with CoPAN, the following evaluations may be useful:
- Neurologic examination for dystonia, rigidity, spasticity and parkinsonism, including formal evaluation of ambulation and speech.
- Screening for developmental assessment, with referral for more formal testing if delay is indicated
- Assessment for physical therapy, occupational therapy, and/or speech therapy and appropriate assistive devices
- Psychiatric assessment for possible obsessive-compulsive behavior.
Management
There is no standard treatment for CoPan and treatments are based on managing symptoms.
Symptomatic treatment is aimed primarily at the dystonia, which can be debilitating. Therapies used with varying success include the oral medications baclofen, anticholinergics, tizanidine, and dantrolene; focal injection of botulinum toxin; intrathecal baclofen; and deep brain stimulation. The symptoms of parkinsonism can be treated with the same medications used in Parkinson’s disease.
More information on these therapies can be found at our Medical Information section of the website.
Attention should be given to swallowing to prevent aspiration and diet with regular measurement of height and weight in children to assure adequate nutrition with gastrostomy tube placement as needed. Assessment of ambulation and speech and communication needs also recommended.
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.
Genetics
CoPan is inherited in an autosomal recessive manner. 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. Statistically, there is a one in four chance that two carriers would have an affected child. There is a two in four chance the parents will have a child who is also a carrier. The chances are one in four that the child will not have the gene 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.
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.
