Propionic Acidemia

Other Names


Propionyl-CoA carboxylase deficiency

Ketotic glycinemia

Ketotic hyperglycinemia

Diagnosis Coding

E71.121, propionic acidemia

Disorder Category

An organic acidemia



Elevated C3 (propionyl carnitine)

Tested By

Tandem mass spectrometry (MS/MS); sensitivity: NA; specificity: NA


Propionic acidemia (PA) is caused by a defect in the mitochondrial enzyme propionyl-CoA carboxylase, which is responsible for converting propionyl-CoA to methylmalonyl-CoA and subsequently to succinyl-CoA that entrs the Krebs cycle. Propionyl-CoA carboxylase is involved in the catabolism of isoleucine, valine, methionine, and threonine, odd-chain fatty acids, cholesterol and nucleotides. The defect results in the accumulation of propionic acid and its metabolites, and a deficiency of Krebs cycle with impaired energy production. PA can is caused by a defect in either of two genes (PCCA and PCCB) that code for the alpha and beta subunits of the enzyme.


About 1:35,000 - 1:75,000 live births; incidence in the Saudi Arabian population is 1:2,000-1:5,000. [Propionic Acidemia - Information for Professionals (STAR-G)]


Autosomal recessive

Prenatal Testing

DNA testing and/or enzyme analysis and/or metabolite testing by amniocentesis.

Other Testing

If the familial mutation is known, DNA testing is possible.

Clinical Characteristics

With treatment, normal development and IQ are possible for patients with milder variants, and symptomatic improvement may be seen in individuals already affected. Without treatment, metabolic crises (severe metabolic acidosis with hyperammonemia) may lead to progressive neurologic injury and death. Symptoms generally begin within the first few days after birth, though in variant forms they may not begin until after 6 weeks of age. Symptoms may be triggered by fasting and illness and children may appear healthy between metabolic crisis episodes. Children with milder variants can present with neurological symptoms or cardiomyopathy, without acute metabolic acidosis. The typical facies of infants with PA includes: frontal bossing, widened depressed nasal bridge, epicanthal folds, long philtrum, upturned curvature of the lips.

Initial signs/symptoms may include:
  • Poor feeding
  • Vomiting
  • Seizures
  • Lethargy progressing to coma
  • Lab findings:
    • Hypoglycemia
    • Metabolic acidosis
    • Hyperammonemia
    • Ketonuria
    • Neutropenia and thrombocytopenia
    • Elevated glycine (usually after the newborn period) in blood and presence of methylcitric acid in urine organic acids

If not treated promptly, recurrent metabolic crises may lead to:
  • Mental retardation
  • Movement disorders
  • Dystonia
  • Spasticity
  • Stroke
  • Brain damage
  • Death

Even with appropriate management, many patients have severe hypotonia and are delayed. Patients have an increased risk of infection, bone marrow suppression, cardiomyopathy and a recurrent pancreatitis.

Treatment consists of a diet low in propiogenic amino acids, carnitine supplementation, prompt treatment of illnesses, and avoidance of fasting. Many of these children reqire placement of a G-tube to facilitate feeding.

Liver transplantation can prevent metabolic crises, but its effect on chronic complications is still unclear. Novel terapeis include the use of N-carbamylglutamate in hyperammonemic crises and chronic anaplerotic supplements (supplements that refll the Krebs cycle).

Follow-up Testing after Positive Screen

Quantitative plasma acylcarnitine profile, plasma amino acids, urine organic acids, plasma total homocysteine, serum vitamin B12 may reveal PA or variants. The most common cause of elevated C3 (mild elevations) is maternal vitamin B12 deficiency.

Primary Care Management

Upon Notification of the + Screen

  • Contact the family and evaluate the infant for poor feeding, lethargy, vomiting, tachypnea.
  • Provide emergency treatment/referral for symptoms of respiratory distress, metabolic acidosis, hypoglycemia, or seizures.
  • Discontinue breast or cow milk formula feeding.
  • To confirm the diagnosis, work with the following service(s): we currently have no Newborn Screening Programs service providers listed, please search our Services database for related services.
  • For evaluation and ongoing collaborative management, consult the following service(s): we currently have no Pediatric Genetics service providers listed, please search our Services database for related services.

If the Diagnosis is Confirmed

  • Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Propionic Acidemia - Information for Parents (STAR-G) for additional information).
  • Frequent low protein, low leucine, low valine, low methionine, low threonine, and high carbohydrate meals may be indicated for affected children (this will usually involve medical formulas and foods).
  • Avoidance of fasting; see the child promptly when illness causes poor p.o. intake.
  • Oral L-carnitine, antibiotics, and biotin may be indicated for some children.
  • Bicarbonate and glucose may be indicated during metabolic crisis episodes.
  • Monitoring of amino acid levels through blood and urine tests and monitoring of ketones through urine tests may be indicated.
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Collaboration

Initial consultation and ongoing collaboration for dietary management, monitoring, and assuring implementation of up-to-date management. Genetic counseling for the family.


Information & Support

For Professionals

Propionic Acidemia - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

Propionic Acidemia (GeneReviews)
Excellent and extensive review by Nuria Carrillo-Carrasco, MD and Charles Venditti, MD, PhD on the GeneReviews site; includes causes, evaluation strategy, genetic counseling, management, resources, and references.

Resources for Propionic Acidemia (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.

Propionic Acidemia (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

National Newborn Screening & Global Resource Center (NNSGRC)
Fact sheets, data reports, publications, and information for clinicians about genetic screening that includes links to state genetic contacts.

Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.

Orphanet is a consortium involving over 40 countries and coordinated in France to provide a portal for information about rare diseases and orphan drugs.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

For Parents and Patients


Propionic Acidemia Foundation
Family support organization site offering information, family stories, frequently asked questions, newsletters, email discussion groups, and other resources.


Propionic Acidemia (Genetics Home Reference)
Excellent, detailed review of the condition for patients and families; sponsored by the U.S. National Library of Medicine.

Propionic Acidemia - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.

Baby's First Test (Genetic Alliance)
A clearinghouse for newborn screening information. Provides resources about screening at the local, state, and national levels and ways for people to share their viewpoints and questions about newborn screening.

Newborn Screening Information for Families (NNSGRC)
Information for families about genetic screening. Links to support groups, advocacy groups, and state genetic contacts; newsletters; factsheets; data reports; and publications; National Newborn Screening and Global Resource Center.

Organic Acidemia Association (OAA)
A nonprofit organization that provides information, newsletters, calendars of events, connections with other parents, a listserv, a discussion board, and nutrition and recipe ideas.

Center for Parent Information and Resources (DOE)
A large resource library related to children with disabilities. Parent Centers in every state provide training to parents of children with disabilities. Lists local conferences, support groups, advocacy tips, and suggestions for finding schools and other local services; Department of Education, Office of Special Education.


ACT Sheet for Elevated C3 Acylcarnitine (ACMG) (PDF Document 352 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithms for Elevated C3 Acylcarnitine (ACMG) (PDF Document)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.

Propionic Acidemia Acute Illness Protocol (NECMP)
A guideline for health care professionals treating the sick infant/child who has previously been diagnosed with propionic acidemia; developed under the direction of Dr. Harvey Levy, Senior Associate in Medicine/Genetics at Children’s Hospital Boston, and Professor of Pediatrics at Harvard Medical School, for the New England Consortium of Metabolic Programs.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

We currently have no Newborn Screening Programs service providers listed; search our Services database for related services.

Pediatric Genetics

We currently have no Pediatric Genetics service providers listed; search our Services database for related services.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for propionic acidemia, last 5 years.

Filipowicz HR, Ernst SL, Ashurst CL, Pasquali M, Longo N.
Metabolic changes associated with hyperammonemia in patients with propionic acidemia.
Mol Genet Metab. 2006;88(2):123-30. PubMed abstract
This study's results suggest that hyperammonemia in propionic acidemia might be related to inability to maintain adequate levels of glutamine precursors through a dysfunctional Krebs cycle.

Schwahn BC, Pieterse L, Bisset WM, Galloway PG, Robinson PH.
Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia.
Eur J Pediatr. 2010;169(1):133-4. PubMed abstract
The authors conclude that NCG should be tried early in acute neonatal hyperammonaemia because it can remove the need for extracorporal detoxification in some cases and can improve long-term outcome.

Vara R, Turner C, Mundy H, Heaton ND, Rela M, Mieli-Vergani G, Champion M, Hadzic N.
Liver transplantation for propionic acidemia in children.
Liver Transpl. 2011;17(6):661-7. PubMed abstract / Full Text
Study conclusion: LT has a role in the management of PA: it reduces the risk of metabolic decompensation and improves the quality of life. The potential for the development of metabolic sequelae is not completely eliminated.


Reviewing Author: Nicola Longo, MD, PhD - 7/2011
Compiled and edited by: Alfred Romeo, RN, PhD - 3/2007
Content Last Updated: 7/2011