Propionic acidemia

Alternate Names

Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; Ketotic glycinemia; PROP; Propionicacidemia

Definition

Propionic acidemia is an inherited condition in which the body can’t breakdown certain parts of proteins and fats. This leads to a build-up of toxic substances and to bouts of serious illness called decompensation events or metabolic crises.

Summary

It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.

Epidemiology

Propionic acidemia affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations worldwide, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians.

Cause

Mutations in the PCCA and PCCB genes cause propionic acidemia. These genes provide instructions for making two parts (subunits) of an enzyme called propionyl-CoA carboxylase, which plays a role in the normal breakdown of proteins. Specifically, this enzyme helps process several amino acids, which are the building blocks of proteins. Propionyl-CoA carboxylase also helps break down certain types of fat and cholesterol in the body. Mutations in the PCCA or PCCB gene disrupt the function of the enzyme and prevent the normal breakdown of these molecules. As a result, a substance called propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

The following includes the most common signs and symptoms in people with propionic acidemia. These features may be different from person to person. Some people may have more symptoms than others and symptoms can vary in severity. The lists do not include every symptom or feature that has been described in this condition. Propionic acidemia causes episodes of illness called decompensation events caused by the build-up of toxic substances in the blood. Decompensation events are serious bouts of illness that can cause brain damage if not treated quickly. Symptoms of a decompensation event usually occur a few days after birth and may include:

• Poor feeding and loss of appetite
• Vomiting
• Weak muscle tone (hypotonia)
• Lack of energy (lethargy)
• Seizures
• Coma

Other complications may include :

• Thickened heart muscle (cardiomyopathy)
• Enlarged liver
• Intellectual and motor disability
• Movement disorders
• Poor growth
• Anemia

In the late-onset form, symptoms appear in childhood and are similar to the neonatal-onset form, but may come and go over time.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Constipation
• Hyperammonemia(High blood ammonia levels)
• Hypoglycemia(Low blood sugar)
• Organic aciduria
• Propionyl-CoA carboxylase deficiency

30%-79% of people have these symptoms

• Abnormality of immune system physiology
• Arrhythmia(Abnormal heart rate)
• Global developmental delay
• Hepatomegaly(Enlarged liver)
• Intellectual disability(Mental deficiency)

5%-29% of people have these symptoms

• Cardiomyopathy(Disease of the heart muscle)
• Cerebellar hemorrhage

Diagnosis

Propionic acidemia can be diagnosed through newborn screening. Almost every state in the United States screens for this disorder. Additional testing required for diagnosis may include:

• Biochemical testing for abnormal levels of specific chemicals
• Genetic testing for mutations in either the PCCA or PCCB gene
• PA is caused by deficiency of propionyl-CoA carboxylase (PCC), the enzyme that catalyzes the conversion of propionyl-CoA to methylmalonyl-CoA. Newborns with PA tested by expanded newborn screening have elevated C3 (propionylcarnitine).
• Testing of urine organic acids in persons who are symptomatic or those detected by newborn screening reveals elevated 3-hydroxypropionate and the presence of methylcitrate, tiglylglycine, propionylglycine, and lactic acid.
• Testing of plasma amino acids reveals elevated glycine.
• Confirmation of the diagnosis relies on detection of biallelic pathogenic variants in PCCA or PCCB or of deficient PCC enzymatic activity. In individuals with equivocal molecular genetic test results, a combination of enzymatic and molecular diagnostics may be necessary.

Treatment

There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. [https:www.ncbi.nlm.nih.gov/books/NBK92946/].

Options include:

• Aggressive treatment of decompensation events
• Special protein managed diet
• Medications such as carnitine
• Avoidance of stressors (such as fasting or illness) that can lead to a decompensation event
• Liver transplant in some cases

Specialists that may be involved in the care of people with propionic acidemia include [1]: Nutritionist

• Genetics professional
• Developmental specialist
• Neurologist
• Physical therapist and occupational therapist

NIH genetic and rare disease info

• NIH info on Propionic acidemia

Propionic acidemia is a rare disease.

Propionic acidemia Resources
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