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Disease Profile

Propionic acidemia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

E71.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Propionyl-CoA carboxylase deficiency; PCC deficiency; Glycinemia, ketotic;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Newborn Screening

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]

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
  • 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.[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.

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.

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

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.

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

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

      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

      Management Guidelines

        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

          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).

            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.

                References

                1. 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.
                2. Shchelochkov OA, Carrillo N and Venditti C. Propionic Acidemia. GeneReviews. Updated Oct 2016; https://www.ncbi.nlm.nih.gov/books/NBK92946/.
                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. 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.
                5. 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/.
                6. Jurecki E, Ueda K, Frazier D, Rohr F, Thompson A, et al.. Nutrition management guideline for propionic acidemia: An evidenceand consensusbased approach. Mol Genet Metab. Apr 2019; 126(4):341-354. https://www.sciencedirect.com/science/article/pii/S1096719218303421?via%3Dihub.

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