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Propionic Acidemia

Last updated Jan. 3, 2019

Approved by: Krish Tangella MD, MBA, FCAP

Propionic Acidemia is a genetic, organic acid disorder in which the body is unable to correctly process proteins and fats, leading to the abnormal buildup of propionyl-CoA in the bloodstream.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Hyperglycinaemia with Ketosis and Leucopenia, Types I and II
  • Ketotic Glycinaemia, Types I and II
  • Methylmalonyl CoA Synthase Deficiency

What is Propionic Acidemia? (Definition/Background Information)

  • Propionic Acidemia is a genetic, organic acid disorder in which the body is unable to correctly process proteins and fats, leading to the abnormal buildup of propionyl-CoA in the bloodstream
  • Propionic Acidemia is inherited in an autosomal recessive pattern. This requires that both parents pass on the abnormal gene to their child
  • Individuals with Propionic Acidemia have mutations in the PCCA and PCCB genes, which provide instructions for making the two parts of the propionyl-CoA carboxylase enzyme
  • When mutations occur, this enzyme is not able to function correctly, which leads to the buildup of harmful levels of propionyl-CoA. Due to this excess buildup, brain and nervous system damage can occur, ultimately leading to life-threatening situations
  • Propionic Acidemia can neither be prevented nor can it be cured. The treatment measures are symptomatic and looks to avoid an excess buildup of propionyl-CoA in the body
  • With proper treatment, the prognosis is better and individuals may lead relatively normal lives. However, without a proper diagnosis and treatment of Propionic Acidemia, it could cause complications, such as metabolic crisis that can even be fatal

Who gets Propionic Acidemia? (Age and Sex Distribution)

  • Propionic Acidemia affects 1 in 35,000-75,000 individuals worldwide
  • Usually, the onset of symptoms occurs within the first few days of birth; though, in some cases, it may begin during childhood
  • Propionic Acidemia affects females at a slightly higher incident rate than males; in a 1.4 : 1 ratio
  • This genetic disorder is more commonly observed in Inuit, Amish, and Saudi Arabian populations, for reasons that are presently unknown

What are the Risk Factors for Propionic Acidemia? (Predisposing Factors)

  • Propionic Acidemia is a genetic disorder that is passed on in an autosomal recessive pattern. If each parent passes on the mutated forms of the PCCA and PCCB gene, then the child will develop the disorder, because it has two sets of the mutations
  • If the child only inherits one copy of the mutated genes, then he/she becomes a carrier and will not develop the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Propionic Acidemia? (Etiology)

  • Propionic Acidemia is an autosomal recessive disorder that is caused by mutations on the PCCA and PCCB gene
  • Normally, these genes are responsible for the instructions that make the two parts of propionyl-CoA carboxylase enzyme. This enzyme helps in breaking down proteins and fats in the body
  • When mutations exist, the enzyme is not able to function correctly and propionyl-CoA builds up in the bloodstream to harmful levels
  • When too much buildup occurs, brain damage, heart abnormalities, nervous system damage, coma, and even death may occur

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Propionic Acidemia?

In most cases, the symptoms of Propionic Acidemia become apparent within a few days of birth. Less commonly, symptoms may also arise during childhood; appearing and disappearing over time.

The signs and symptoms of Propionic Acidemia include:

  • Poor feeding
  • Vomiting
  • Lethargy
  • Hypoglycemia
  • Hyperammonemia - increased amounts of ammonia in blood
  • Ketonuria - increased amount of ketones in urine
  • Elevated glycine levels
  • Metabolic crisis, leading to:
    • Seizures
    • Brain damage
    • Mental retardation
    • Heart abnormalities
    • Movement disorders

How is Propionic Acidemia Diagnosed?

Propionic Acidemia can be diagnosed using a variety of tests and exams. These include:

  • Physical examination with medical and family history evaluation
  • Urine tests are commonly conducted to determine the presence of organic acids that are not normally present in urine
  • Similarly, amino acid plasma tests can be conducted to determine, if there are elevated levels of glycine in the body
  • To confirm the initial diagnosis of Propionic Acidemia, genetic testing should be conducted to determine, if mutations exist in the PCCA and PCCB genes

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Propionic Acidemia?

The following complications may be noted with Propionic Acidemia:

  • Metabolic crisis often occur in individuals with Propionic Acidemia. When too much propionyl-CoA builds up in the bloodstream, metabolic crisis is triggered and fatal complications may occur
  • Often times, brain damage, mental retardation, heart abnormalities, optic atrophy, and hearing loss, may occur

In extreme cases, death may result from these complications.

How is Propionic Acidemia Treated?

Currently, there is no cure for Propionic Acidemia. If a child is born with the disorder, signs and symptoms of the disorder will exist throughout their life. In order to lessen the severity of symptoms, prompt treatment and management of Propionic Acidemia is essential.

  • Most healthcare providers would suggest that those affected by Propionic Acidemia minimize their protein intake, to prevent excess buildup of propionyl-CoA in the body
  • L-carnitine supplements may also be prescribed
  • Liver transplantation may help prevent metabolic crises and ease the symptoms of Propionic Acidemia. However, more research must be done to confirm this

How can Propionic Acidemia be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Propionic Acidemia genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Propionic Acidemia? (Outcomes/Resolutions)

  • Individuals with Propionic Acidemia will be affected throughout their life and there is no cure for the condition
  • If a diagnosis is made early in life and early treatment started, normal development is possible. With regular treatment, symptoms can be minimized and the affected individuals will be able to lead relatively normal lives
  • On the other hand, if no suitable treatment is provided, it may lead to frequent metabolic crises that can cause progressive neurologic injury, leading to death

Additional and Relevant Useful Information for Propionic Acidemia:

The following DoveMed website link is a useful resource for additional information:


What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Nov. 1, 2014
Last updated: Jan. 3, 2019