Are there any new, effective treatments for propionic acidemia?
Dr. Greene’s Answer:
Propionic acidemia is an error in protein metabolism. Every time we eat food that contains protein, our bodies use a series of enzymes to break those huge foreign protein molecules into small pieces. These then become the building blocks we reassemble to form the specific human proteins we need.
In people with propionic acidemia, there is an insufficient supply of one of these enzymes (propionyl coenzyme A [CoA] carboxylase). Without the propionyl CoA carboxylase, there is a bottleneck in protein processing. Propionic acid builds up in the blood. This is known to damage the lining of small blood vessels, allowing the propionic acid to leak into the brain and nerve tissues, where it alters behavior and development. Ammonia also accumulates in the blood. This too can damage the brain. Food that is meant to nourish becomes a poison.
The great news is that truly curing this disease-not just treating it-may be around the corner! Gene therapy is one method scientists have explored. In gene therapy, a missing or nonfunctioning gene is replaced by a new, functioning gene. In the laboratory, gene therapy for propionic acidemia has already worked (Am J Hum Genet Oct 2007). The hope is bright that within a few years the defect may be curable in humans. Successful gene therapy will not reverse brain or nerve damage but can stop any further damage from occurring-giving the child a chance to grow unfettered. Coupled with important advances in early diagnosis-possible now even before a baby is born – the potential is huge.
Auxiliary liver transplant is another strategy that has been explored for the treatment of inborn errors of metabolism. Affected children are essentially given an extra liver! The donated liver supplies enough of the missing protein to restore normal metabolism. Such transplants in children with propionic acidemia have been so successful that, in some cases, a protein-restricted diet was no longer needed.