Propionic acidemia

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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:

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

Summary Summary

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 pattern. Diagnosis is based on the symptoms, clinical exam, blood and urine testing, and may be confirmed by the results of genetic testing. Treatment includes aggressive management of decompensation events, a special protein-restricted diet and medications.^[1]^[2]

Last updated: 1/26/2020

Symptoms 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.^[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 ^[2]:

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

In the late-onset form, symptoms appear in childhood and are similar to the neonatal-onset form, but may come and go over time.^[2]

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.^[1]^[4] Other possible long-term complications can include poor growth, kidney failure, and liver problems.

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.

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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 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 1/1/2021

Cause Cause

Propionic acidemia occurs when either the PCCA or PCCB genes is not working correctly.^[2] DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.

Last updated: 1/26/2020

Inheritance Inheritance

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.^[2]

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

Diagnosis 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:^[2]^[5]

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.

Treatment Treatment

There is no specific treatment for propionic acidemia. Treatment is focused on managing the symptoms. Options include:^[1]

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

Last updated: 1/26/2020

Management Guidelines

Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, et. al. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014 Sep 2;9:130.

Statistics Statistics

It is estimated that between about 1/105,000-1/240,000 babies are born with propionic acidemia in the United States.^[5]

Last updated: 1/26/2020

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Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

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 Research

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.

Organizations Organizations

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

Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
Organic Acidemia Association
9040 Duluth Street
Golden Valley, MN 55427
Telephone: 763-559-1797
Fax: 866-539-4060
E-mail: mkstagni@gmail.com
Website: http://www.oaanews.org/
Propionic Acidemia Foundation
1963 McCraren Rd.
Highland Park, IL 60035
Toll-free: 877-720-2192
E-mail: paf@pafoundation.com
Website: http://www.pafoundation.com/

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).

Do you know of an organization? We want to hear from you.

Learn More Learn More

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.

GARD Answers GARD Answers

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Have a question? Contact a GARD Information Specialist.

References References

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.
Shchelochkov OA, Carrillo N and Venditti C. Propionic Acidemia. GeneReviews. Updated Oct 2016; https://www.ncbi.nlm.nih.gov/books/NBK92946/.
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.
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.
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/.
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.