Home > Newborn Disorders > Propionic acidemia
Propionic acidemia
Names
Propionic acidemia
PA
Propionyl-CoA carboxylase deficiency
Ketotic glycinemia
Ketotic hyperglycinemia
Overview
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.Prevalence
About 1/35,000 - 1/75,000 live births; incidence in the Saudi Arabian population is 1/2,000-1/5,000. [Propionic acidemia info for professionals (STAR-G)]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 on positive screening test
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): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
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 info 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.Resources
Information & Support
For Professionals
Propionic acidemia info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
ACT Sheet for Elevated C3 Acylcarnitine (ACMG)
(
352 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Propionic acidemia Emergency Protocol
A guideline for healthcare 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.
Organic Acidemias (GeneReviews)
Excellent and extensive review by Margretta Seashore, MD on the GeneReviews site; includes causes, evaluation strategy, genetic
counseling, management, resources, and references.
Resources for propionic acidemia (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Propionic acidemia (OMIM)
From the Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University, providing technical information for
providers on genetic disorders, links to MEDLINE, and links to other scientific information and sites.
For Parents and Patients
Support
Propionic Acidemia Foundation
Family support organization site offering information, family stories, frequently asked questions, newsletters, email discussion
groups, and other resources.
General
Propionic acidemia info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about propionic acidemia
and links to other sites including parent support groups.
Propionic acidemia (Genetics Home Reference)
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Organic Acidemia Association (OAA)
A non-profit organization that provides information for parents and providers; newsletters; event information; connections
with other parents; a listserv; a discussion board; information about nutrition and recipes; translation of their web pages
into five other languages; hosting of the Propionic Acidemia Research Network and other research funds; and links to other
sites.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Helpful Articles
PubMed search for articles on propionic acidemia in the 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 / Full Text
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 / Full Text
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.
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 7/2011 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 7/2011 |