Propionic acidemia

Title

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 that occurs when the body is unable to process certain parts of proteins and lipids (fats) properly. As a result, abnormal levels of toxic substances build up in the blood and tissues, which can cause serious health problems. Signs and symptoms of the condition generally develop within the firsts few days after birth and may include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). Without early diagnosis and treatment, these symptoms may progress to more serious medical problems, such as heart abnormalities, seizures, 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 generally includes a special diet and addressing symptoms during a metabolic crisis.^[2]

Last updated: 12/2/2015

Symptoms Symptoms

Propionic acidemia causes episodes of illness called metabolic crises. This is a serious health condition caused by the build-up of toxic substances in the blood.^[3]

Most of the time, individuals with propionic acidemia have symptoms within a few days after they are born (neonatal-onset). They usually experience poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). Sometimes symptoms can become more serious and lead to heart abnormalities, seizures, coma, and possibly death.^[1]

There is another form of propionic acidemia that is less common and the symptoms appear during childhood (late-onset). The symptoms are similar to the neonatal-onset form of this disorder, but the symptoms may also come and go over time. More serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections. Some children with this form of propionic acidemia experience intellectual disability, delayed development, or developmental regression (where the child looses skills over time).^[1]

Last updated: 12/9/2015

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Constipation	Very frequent (present in 80%-99% of cases)
Hyperammonemia	Very frequent (present in 80%-99% of cases)
Hypoglycemia	Very frequent (present in 80%-99% of cases)
Organic aciduria	Very frequent (present in 80%-99% of cases)
Propionyl-CoA carboxylase deficiency	Very frequent (present in 80%-99% of cases)
Abnormality of immune system physiology	Frequent (present in 30%-79% of cases)
Arrhythmia	Frequent (present in 30%-79% of cases)
Hepatomegaly	Frequent (present in 30%-79% of cases)
Intellectual disability	Frequent (present in 30%-79% of cases)
Cardiomyopathy	Occasional (present in 5%-29% of cases)
Cerebellar hemorrhage	Occasional (present in 5%-29% of cases)
Acute encephalopathy	-
Anemia	-
Apnea	-
Autosomal recessive inheritance	-
Cerebral atrophy	-
Coma	-
Dehydration	-
Dystonia	-
Eczema	-
Failure to thrive	-
Feeding difficulties in infancy	-
Hyperglycinemia	-
Hyperglycinuria	-
Lactic acidosis	-
Lethargy	-
Limb hypertonia	-
Metabolic acidosis	-
Muscular hypotonia of the trunk	-
Neutropenia	-
Osteoporosis	-
Pancreatitis	-
Pancytopenia	-
Poor appetite	-
Seizures	-
Tachypnea	-
Thrombocytopenia	-
Vomiting	-

Last updated: 9/1/2017

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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

Appropriate dietary management is the main treatment for propionic acidemia. It is recommended that individuals with propionic acidemia consume a low-protein diet. This helps prevent a metabolic crisis. Several commercially produced formulas are available that provide a protein supplement without any of the 4 amino acids that result in propionate production.^[2]^[3] However, since these amino acids are essential for human development, closely monitored quantities will need to be added. This should be done with the guidance of a biochemical geneticist and a nutritionist.^[2] Some physicians recommend oral biotin or carnitine supplementation, although more research is needed to determine the effectiveness of these treatments.^[2]^[3] It is also important for individuals with propionic acidemia to avoid going a long time without food (fasting). Fasting may cause a metabolic crisis. Children who are having symptoms of a metabolic crisis should be treated in the hospital where they may be given medications such as bicarbonate or glucose.^[3]

Last updated: 12/22/2015

Management Guidelines

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.
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.

Prognosis Prognosis

Babies who receive prompt and ongoing treatment before they experience a metabolic crisis may have normal growth and development. The outcome is generally better with early treatment. However, some children have life-long learning problems, cognitive deficiency, seizures, or problems with involuntary movements, even with treatment.^[3] Children with a classic presentation and course generally have a guarded prognosis, meaning they are typically stable but there is a potential for serious issues, especially if they have a metabolic crisis. In severe cases, survival may be threatened, particularly in the presence of severe brain damage.^[4]

Last updated: 12/22/2015

Do you have updated information on this condition? Let us know.

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 studying or have studied 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

Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
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).

Parent Matching Organizations

The Organic Acidemia Association helps connect the parents of children with organic acidemias.

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

GARD Answers GARD Answers

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. Submit a new question

My cousin has been treated since birth for propionic acidemia. She has not responded to treatment and has experienced many side-effects. What treatments are available for this condition? What is the prognosis? See answer
Does propionic acidemia carry risk factors for hearing loss, especially progressive hearing loss? See answer

Have a question? Contact a GARD Information Specialist.

References References

Propionic acidemia. Genetics Home Reference. July 2007; http://ghr.nlm.nih.gov/condition/propionic-acidemia.
Karl S Roth. Genetics of Propionic Acidemia (Propionyl CoA Carboxylase Deficiency). Medscape Reference. November 2014; http://emedicine.medscape.com/article/948084-overview.
Propionic Acidemia. Screening, Technology and Research in Genetics (STAR-G). 2008; http://www.newbornscreening.info/Parents/organicaciddisorders/PA.html#4. Accessed 3/30/2011.
Karl S Roth. Propionic Acidemia (Propionyl CoA Carboxylase Deficiency): Follow-up. eMedicine. 2009; http://emedicine.medscape.com/article/948084-followup. Accessed 3/30/2011.