Dr. Greene's Answer
Propionic acidemia is what we call an inborn error of metabolism. Our bodies use detailed blueprints (our genes) to guide the manufacture of the proteins and enzymes we need to carry out the processes of life. Errors in these genes can lead either to a lack of necessary proteins or to the accumulation of toxic substances.
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.
Propionic acidemia is really more than one disease, depending on the extent of the enzyme deficiency. In some people, the defect is complete, with the early onset of severe symptoms. At the other end of the spectrum, one man had such a mild deficiency that he didn’t develop symptoms until he was 31 years old!
In general, those with intermediate levels of enzyme deficiency have symptoms that come in separate attacks when levels of protein to be digested are out of balance with the amount of enzyme available. This might be caused by a high-protein diet’s increasing the protein to be digested, or by stress or illness, decreasing enzyme production. Constipation can also trigger an attack because it increases dietary protein available for processing and because gut bacteria can produce additional propionic acid. These attacks can cause a rapid downward spiral in a child’s condition because the vomiting child with poor appetite, desperate for calories, will begin to process his own protein for food, leading to increasing levels of acid.
Long-term treatment includes a low-protein diet (1.0-1.5 g/kg/24 hr). Synthetic proteins deficient in key amino acids (isoleucine, valine, threonine, and methionine) are used to increase the amount of dietary protein (to 1.5-2.0 g/kg/24 hr) while causing minimal change in propionic acid production. Still, natural proteins should comprise most (50-75%) of the dietary protein.
L-carnitine supplementation (50-100 mg/kg/24 hr orally) is also a part of long-term treatment. And thiamin deficiency has been shown to make propionic acidemia worse. Early vitamin supplementation is a good idea for these children-and especially when having an attack.
Close monitoring of blood pH, amino acids, urinary content of propionate and its metabolites, and growth curves is necessary to adjust the proper balance of the diet and ensure the success of therapy. Some patients may require chronic alkaline therapy to correct low-grade chronic acidosis. Also, children with propionic acidemia are especially prone to infections. Any infection should be treated promptly.
Long-term prognosis is guarded-especially in those who develop symptoms in the first week of life. Seizures occur in about 30% of affected infants. Survival has been improving dramatically in recent years, but death may still occur during an acute attack. Normal development is possible, but most children do have some degree of permanent developmental deficit.