National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Propionic acidemia


Other Names:
Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic; Hyperglycinemia with ketoacidosis and leukopenia; Ketotic hyperglycinemia; Ketotic glycinemia; PROP; Propionicacidemia See More
Categories:
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. Symptoms of a decompensation event include poor feeding, vomiting, weak muscle tone (hypotonia), and lack of energy (lethargy). This usually occurs within the first few days after birth. Without early diagnosis and treatment, these symptoms may lead  to more serious medical problems, including heart abnormalities, seizures, intellectual disability, coma, and possibly death. Propionic acidemia is caused by changes (mutations) in the PCCA and PCCB genes and is inherited in an autosomal recessive manner.[1] Treatment  includes aggressive management of decompensation events, a special protein-restricted diet and medications.[2] 
Last updated: 1/26/2020
Propionic acidemia causes episodes of illness called decompensation events caused by the build-up of toxic substances in the blood.[3] 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 [1]:
  • 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.[1]
Last updated: 1/26/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 42 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Constipation 0002019
Hyperammonemia
High blood ammonia levels
0001987
Hypoglycemia
Low blood sugar
0001943
Organic aciduria 0001992
Propionyl-CoA carboxylase deficiency 0003353
30%-79% of people have these symptoms
Abnormality of immune system physiology 0010978
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Global developmental delay 0001263
Hepatomegaly
Enlarged liver
0002240
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
5%-29% of people have these symptoms
Cardiomyopathy
Disease of the heart muscle
0001638
Cerebellar hemorrhage 0011695
Percent of people who have these symptoms is not available through HPO
Acute encephalopathy 0006846
Anemia
Low number of red blood cells or hemoglobin
0001903
Apnea 0002104
Autosomal recessive inheritance 0000007
Cerebral atrophy
Degeneration of cerebrum
0002059
Coma 0001259
Dehydration 0001944
Dystonia 0001332
Eczema 0000964
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Feeding difficulties in infancy 0008872
Hyperglycinemia
Elevated blood glycine levels
0002154
Hyperglycinuria
High urine glycine levels
0003108
Increased level of hippuric acid in urine 0410066
Lactic acidosis
Increased lactate in body
0003128
Lethargy 0001254
Limb hypertonia
Increased muscle tone of arm or leg
0002509
Metabolic acidosis 0001942
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Neutropenia
Low blood neutrophil count
Low neutrophil count
[ more ] 		0001875
Osteoporosis 0000939
Pancreatitis
Pancreatic inflammation
0001733
Pancytopenia
Low blood cell count
0001876
Poor appetite
Decreased appetite
0004396
Psychomotor retardation 0025356
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Tachypnea
Increased respiratory rate or depth of breathing
0002789
Thrombocytopenia
Low platelet count
0001873
Vomiting
Throwing up
0002013
Showing of 42 |
Last updated: 7/1/2020
Propionic acidemia is caused by changes in the PCCA and PCCB genes.[1]
Last updated: 1/26/2020
Propionic acidemia is inherited in an autosomal recessive pattern.  All individuals inherit two copies of each gene. To have propionic acidemia, a person must have a mutation in both copies of either the PCCA or PCCB gene.[1]

People with autosomal recessive conditions inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a: 
  • 25% (1 in 4) chance to have the disorder
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% (1 in 4) chance to be unaffected and not be a carrier. 
Last updated: 1/26/2020
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:[1][4]
  • Biochemical testing for abnormal levels of specific chemicals
  • Genetic testing for mutations in either the PCCA or PCCB gene   
Last updated: 1/26/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • An Algorithm flowchart is available for this condition for determining the final diagnosis in an infant with a positive newborn screening result. Algorithms are developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.
There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. Options include:[2]
  • 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 [2]: 
  • Nutritionist
  • Genetics professional
  • Developmental specialist
  • Neurologist
  • Physical therapist and occupational therapist
Last updated: 1/26/2020

Management Guidelines

The long-term outcome in propionic acidemia varies from person to person. In general, early diagnosis and treatment, especially before a decompensation event occurs, is associated with a better outcome. Some children have life-long learning problems, intellectual disability, seizures, or problems with involuntary movements, even with treatment.[2][5] Other possible long-term complications can include poor growth, kidney failure, and liver problems.
Last updated: 1/26/2020
It is estimated that between about 1/105,000-1/240,000 babies are born with propionic acidemia in the United States.[4]
Last updated: 1/26/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes neonatal sepsis, other branched chain organic acidurias, pyloric stenosis or other common causes of increased anion gap acidosis. In the infantile chronic form, failure to thrive, chronic vomiting and neutropenia may mimic cow milk intolerance, celiac disease (see this term) or immune deficiencies.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Propionic acidemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Baby's First Test offers an information page on Propionic acidemia.
  • Genetics Home Reference (GHR) contains information on Propionic acidemia. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
  • The Screening, Technology And Research in Genetics (STAR-G) Project has a fact sheet on this condition, which was written specifically for families that have received a diagnosis as a result of newborn screening. This fact sheet provides general information about the condition and answers questions that are of particular concern to parents.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • The New England Consortium of Metabolic Program has written medical guidelines called acute care protocols for Propionic acidemia for health care professionals. 
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Propionic acidemia. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Shchelochkov OA, Carrillo N and Venditti C. Propionic Acidemia. GeneReviews. Updated Oct 2016; https://www.ncbi.nlm.nih.gov/books/NBK92946/.
  2. Haijes HA, van Hasselt PM, Jans JJM, Verhoeven-Duif NM. Pathophysiology of propionic and methylmalonic acidemias. Pt 2: Treatment strategies. J Inherit Metab Dis. Sept 2019; 42(5):745-761. https://www.ncbi.nlm.nih.gov/pubmed/31119742.
  3. Haijes HA, Jans JJM, Tas SY, Verhoeven-Duif NM, van Hasselt PM. Pathophysiology of propionic and methylmalonic acidemias. Pt 1: Complications. J Inherit Metab Dis. Sept 2019; 42(5):730-744. https://www.ncbi.nlm.nih.gov/pubmed/31119747.
  4. Almasi T, Guey LT, Lukas C, Csetneki K, Voko Z, Zelei T. Systematic literature review and meta-analysis on the epidemiology of propionic acidemia. Orphanet Jl of Rare Dis. Feb 13, 2019; 14(1):40. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375193/.
  5. Haijes HA, Molema F, Langeveld M, Janssen MC, Bosch AM, van Spronsen F, et al. Retrospective evaluation of the Dutch pre-newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening. J Inherit Metab Dis. Dec 11, 2019; Epub ahead of print. https://www.ncbi.nlm.nih.gov/pubmed/31828787.
  6. Jurecki E, Ueda K, Frazier D, Rohr F, Thompson A, et al.. Nutrition management guideline for propionic acidemia: An evidence- and consensus- based approach. Mol Genet Metab. Apr 2019; 126(4):341-354. https://www.sciencedirect.com/science/article/pii/S1096719218303421?via%3Dihub.