NIH PA Study

Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia

Charles Venditti MD PhD

Oleg Shchelochkov MD

National Institutes of Health

Why are we doing this study?

Propionic acidemia (PA) is one of the most common disorders of organic acid metabolism. Newborn screening for propionic acidemia allows doctors start treatment at an early age. However, despite early and intense medical treatment, many patients experience health problems. Patients can have frequent hospitalizations for metabolic crises and develop chronic medical issues such as brain, eye, heart, abdomen, and kidney problems.

To help better understand the health problems patients with propionic acidemia have, we are starting a new study: “Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia.” This study will evaluate patients with propionic acidemia to learn more about the genetic and biochemical causes and the medical complications associated with it.  We also plan to study how bacteria living in our gut (microbiome) can affect the course of propionic acidemia.

How can patients participate in this study and what will happen during the visit?

Eligible patients will be admitted to the NIH Clinical Center for 3-5 days. Most travel expenses are covered for patients and their care providers. A typical visit will involve a medical interview, physical examination, genetic counseling and consultation with experts in different fields, such as the nervous system, nutrition, rehabilitation medicine and other areas of medicine. Patients will be asked to provide blood, urine and stool samples to help measure function of organs affected by propionic acidemia. We use imaging studies such as X-ray and ultrasound to look for changes in organs inside the body. We may offer additional tests to some patients.

How can I find out more about this study?

You can find our more about this study by visit our the Propionic Acidemia Clinical Trials webpage

Contact information

If you are interested in learning more about the study please contact us:

[email protected]


NIH Clinical Center Patient Recruitment and Public Liaison Office



Propionic Acidemia Genetics Part 1

PA Genetics, Part 1


Propionic Acidemia (PA) is a condition caused by changes in the genes that make the propionyl-coenzyme A (CoA) carboxylase enzyme. Genes are made of DNA which is our hereditary material. Genes have the instructions that tell our bodies how to grow and function. Each gene provides specific instructions for various biological processes in the body.


The genes that make the propionyl CoA carboxylase enzyme are called PCCA and PCCB. The enzyme helps break down certain proteins and fats from food to make into chemical energy and other products the body needs. When there is a change in the gene called a mutation, the genes cannot perform their normal function.  If these genes do not work and the body cannot break down fats and proteins, there is a buildup of organic acids in the body which can cause the symptoms associated with PA such as vomiting, weak muscle tone, and developmental delays.


If someone has a mutation, it is something he or she was born with. These mutations happen randomly and they are not caused by something the person did. We have two copies of each gene. We inherit one copy from each parent. If someone has one gene with a mutation and one gene that works properly, they are called a carrier. Carriers do not have symptoms of propionic acidemia because having one working gene copy means the body is still able to break down fats and proteins.


If both parents are carriers of propionic acidemia, there is a 1 in 4 or 25% chance of having a child with propionic acidemia. This is called autosomal recessive inheritance.  The condition can affect males and females and an individual has to inherit two mutated genes to be affected with PA.  Therefore, in order to be affected by PA, the child has to inherit a gene mutation from both parents. If a child inherits one working gene and one mutated gene, they will also be a carrier of

PA and will not have symptoms.  If a child inherits both normal copies of

the gene, they will not be a carrier and not have the condition.



To find out if you are a carrier of PA, you can have genetic testing. Our DNA is written in a four-letter code. Genetic testing works by reading through the code like a spellchecker looking for a change, also called a mutation.


Robyn Hylind

Genetic Counseling Student

Northwestern University

Graduate Program in Genetic Counseling