An Overview of Propionic Acidemia

A rare genetic cause of severe illness in newborns

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Propionic acidemia is a rare and serious genetic disorder that affects multiple systems of the body, including the brain and heart. Without prompt diagnosis and treatment, it can cause coma and even death. Due to a genetic defect, the body is unable to properly process certain parts of proteins and fats. This ultimately leads to the symptoms of the condition.

It is a rare disease, estimated to occur in around one in 100,000 infants in the US. However, it may be slightly more common in certain populations, such as in people from Saudi Arabia.

Symptoms

Most often, the symptoms of propionic acidemia appear within a few days of birth. Infants are born healthy, but symptoms such as poor feeding and decreased responsiveness soon occur. Without prompt diagnosis and treatment, additional symptoms appear:

Common Symptoms

  • Worsening lethargy
  • Decreased muscle tone
  • Seizures
  • Vomiting
  • Coma

Without diagnosis and acute intervention, death may soon follow.

Less commonly, symptoms might first appear later in childhood, or in adolescence or adulthood. Whenever it begins, propionic acidemia can also lead to more chronic problems:

Chronic Problems

  • Decreased overall growth
  • Developmental delay and intellectual disability
  • Seizures
  • Gastrointestinal symptoms
  • Pancreatitis
  • Movement disorders
  • Cardiomyopathy
  • Kidney failure
  • Hearing loss
  • Osteoporosis
  • Optic atrophy (leading to vision loss)
  • Premature ovarian failure
  • Blood problems (like decreased numbers of certain immune cells and anemia)

However, it is important to note that not everyone with propionic acidemia will experience all these symptoms. Symptom severity also varies.

Many of these symptoms of the condition may wax and wane over time, with periodic worsening. These periods of more serious illness may be triggered by fasting, fever, vomiting, infection, surgery, physical or emotional stress, or by failing to follow the recommended treatments. This is called “decompensation” of the illness, and it can lead to coma and other life-threatening problems.

Causes

Propionic acidemia is a type of “inborn error of metabolism.” These are a group of individually rare diseases caused by different genetic defects. These lead to problems with metabolism, the process by which the nutrients in food are turned into energy.

Metabolism takes place through a complicated and highly coordinated sequence of chemical reactions, so problems in many different genes can lead to some sort of disruption of normal metabolic processes.

Propionic acidemia also belongs to a smaller subset of these diseases called organic acidurias. These genetic diseases result from difficulties metabolizing certain types of amino acids (the building blocks of protein) as well as some components of carbohydrates and fats. Because of this, the levels of certain acids normally present in the body may begin to rise to unhealthy levels.

Defects in different enzymes lead to different types of organic aciduria. For example, maple syrup urine disease is another rare disease in this class. Other rare diseases in this group may have some similar symptoms.

Propionic acidemia is caused by a defect in one of two genes: PCCA or PCCB. These two genes make up the two components of an enzyme called propionyl-CoA carboxylase (PCC). This enzyme normally catalyzes one of the important steps in metabolizing certain amino acids, as well as some other important compounds, like certain components of fats and cholesterol.

When there is a genetic defect in either of the genes PCCA or PCCB, the enzyme PCC works poorly or not at all. Because of this, propionic acid begins to accumulate, as well as some other related substances. These compounds can be toxic when they build up in the body, leading to some of the symptoms of the disease.

Other symptoms may result because of dysfunctions in energy production resulting from the problem with this step of metabolism.

Diagnosis

Diagnosis of propionic acidemia requires a thorough medical history and medical exam, as well as laboratory testing. It’s important that diagnosis happen as quickly as possible since affected individuals are often very ill.

Many different types of medical problems can lead to the neurological and other symptoms seen in decompensated propionic acidemia, including other rare genetic diseases. Medical practitioners must rule out these other possible diagnoses while they narrow in on the specific cause. It’s important that practitioners consider propionic acidemia in any infant with potential signs of the condition.

Lab Tests

A wide range of laboratory tests are usually needed. Some of these might include:

  • Basic blood work (to assess for response to infection, anemia, glucose levels, basic organ function, etc.)
  • Blood work to assess various metabolites such as ammonia, lactic acid
  • Blood sample to assess for bacterial infection
  • Urinalysis (to assess for metabolites and infection)

People with propionic acidemia may also have abnormalities in more specialized tests. For example, people with the condition will show an elevation in a substance called propionylcarnitine.

Based on these initial tests, doctors work to confirm the diagnosis. This might include tests to assess how well the PCC enzyme is working. Genetic tests of the PCCA and the PCCB genes can also be used to finalize the diagnosis.

Sometimes, infants are first diagnosed from the results of standard newborn screening tests. However, not all states or countries around the world test for this specific disease. Also, infants may first experience symptoms before the results of these screening tests are available.

Newborn Screening for Genetic and Metabolic Disorders

Treatment

Periods of acute illness from propionic acidemia are medical emergencies. Without support, individuals may die during these decompensations. These may occur before an initial diagnosis or at other periods of stress or illness. These individuals need intensive support in a hospital setting.

Possible Support Needed

Individuals with propionic acidemia might need interventions like the following:

  • Intravenous fluids and glucose
  • Treatment of precipitating factors (like bacterial infection)
  • Tightly managed protein intake
  • Intravenous carnitine (enhances removal of propionic acid through the urine)
  • Medications such as sodium benzoate (to remove toxic byproducts)
  • Ventilatory support, if necessary
  • Hemodialysis or extracorporeal membrane oxygenation (ECMO, to remove toxic byproducts)

Over the long-term, dietary management is a cornerstone of treatment for propionic acidemia. These individuals should work closely with a dietary specialist experienced in rare metabolic diseases.

By limiting the intake of protein, one can reduce the impact of the disease. However, limiting protein too severely has its own negative health impacts. So, an individual with the condition needs ongoing contact with a medical provider who can help make specific dietary recommendations, which may change over time. A feeding tube is also sometimes helpful to help ensure proper nutrition, especially during decompensations.

Potential long-term medications include:

  • L-carnitine
  • Metronidazole (reduces production of propionate by normal gut bacteria)

In some cases, a liver transplant is also an option. This might be particularly helpful for patients who experience frequent decompensations.

People with propionic acidemia may also need treatment for complications of the disease. For example, medications for seizures might be needed, or interventions to treat pancreatitis.

Another important aspect of treatment is preventing decompensations. Affected individuals need to be closely monitored whenever they are exposed to stressors that might trigger an exacerbation. That way, treatment can begin promptly if necessary.

Individuals also need to be educated to avoid fasting and other potential stressors. Some patients may also need to monitor their urine for ketones, a metabolic byproduct that may be a sign of decompensation.

People with propionic acidemia also need regular monitoring for long-term complications of the condition. For example, this should include regular eye exams, hearing evaluations, and cardiology assessments. They will also need regular blood tests to help monitor their condition and the status of possible complications.

Ideally, people with propionic acidemia should see a specialist with experience in rare genetic diseases. Treatment and monitoring will require a range of medical professionals working together as a team.

Inheritance

Propionic acidemia is an autosomal recessive genetic condition. That means that a person has to inherit an affected gene from both of their parents to get the disease.

If a couple has had one child born with propionic acidemia, there is a 25 percent chance that their next child would also have the condition. It’s also important to test existing siblings for the disease since not all people with propionic acidemia display symptoms at birth. Early diagnosis and management may then help prevent long-term complications from the disease.

Talking with a genetic counselor can be very helpful for many families. This can give you a sense of the risks in your situation. Prenatal testing and embryo selection may also be an option.

How Genetic Disorders Are Inherited

A Word From Verywell

It can feel devastating to learn that your child has a condition like propionic acidemia. Often the initial diagnosis occurs during a life-threatening health crisis in the first few days of life, which is understandably overwhelming for most families. It can take a while to process what is happening. Know that your child has a team of health professionals to aid in their short-term recovery and long-term health. Propionic acidemia is a disease with risks requiring ongoing management, however, many people with the condition go on to lead full lives. Don’t hesitate to reach out to your friends, family members, and healthcare team to get the support you need.

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