Propionic Acidemia
Guidance for primary care clinicians receiving a positive newborn screen result
Description
Propionic acidemia is caused by a deficiency of the propionyl-CoA carboxylase, the enzyme responsible for converting propionyl-CoA to methylmalonyl-CoA and subsequently to succinyl-CoA as it enters the Krebs cycle. This defect in protein and fat metabolism results in the accumulation of propionic acid and other organic acid by-products, which have a toxic effect on multiple other metabolic processes. Affected individuals typically present within the first few days of life with poor feeding, lethargy, neutropenia, thrombocytopenia, severe metabolic acidosis, hypoglycemia, hyperammonemia, and progressive encephalopathy. Late complications include cardiomyopathy, renal disease, pancreatitis, and optic atrophy. A much more rare late onset form of propionic acidemia presents with failure to thrive, intermittent vomiting, hypotonia, movement disorders, seizures, cardiomyopathy, and developmental delays or regression.
Clinical Characteristics
- Poor feeding
- Vomiting
- Seizures
- Lethargy
- Lab findings:
- High anion gap metabolic acidosis
- Hyperammonemia
- Ketonuria
- Hypoglycemia
- Neutropenia and thrombocytopenia
- Elevated C3 (propionylcarnitine) and glycine in blood
- Elevated 3-hydroxypropionate, propionylglycine, tiglylglycine, and methylcitric acid in urine
- Intellectual disability
- Failure to thrive
- Movement disorders
- Dystonia
- Developmental regression
- Death
Primary Care Management
Next Steps After a Positive Screen
- Contact the family and evaluate the infant for poor feeding, lethargy, vomiting, and tachypnea.
- Consult with a pediatric metabolic specialist immediately.
- Provide emergency treatment/referral for symptoms of respiratory distress, metabolic acidosis, hypoglycemia, seizures, dehydration, ketonuria, hyperammonemia, or failure to thrive.
Confirming the Diagnosis
- To confirm the diagnosis, work with Newborn Screening Services (see NW providers [1]).
- Follow-up testing may include quantitative plasma acylcarnitine profile, plasma amino acids, urine organic acids, plasma total homocysteine, and serum vitamin B12. The most common cause of elevated C3 (mild elevations) is maternal vitamin B12 deficiency.
- Diagnosis confirmation may require molecular genetic testing.
If the Diagnosis is Confirmed
- For evaluation and ongoing collaborative management, consult Biochemical Genetics (Metabolics) (see NW providers [1]).
- Refer for initial consultation and ongoing collaboration of dietary management. See Nutrition, Metabolic (see NW providers [11]).
- Refer the family to Genetic Testing and Counseling (see NW providers [6]) if not already done.
- 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).
- Avoid fasting; see the child promptly when illness causes poor intake.
- Refer for cognitive/behavioral testing and development assessment. See Developmental Assessments (see NW providers [1]).
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Resources
Information & Support
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive
for a newborn condition. Find information about A New Diagnosis - You Are
Not Alone; Caring for Children with Special Health Care Needs; Assistance in
Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to
Do After a Diagnosis.
For Professionals
Propionic Acidemia (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular
pathogenesis; from the University of Washington and the National Library of Medicine.
Propionic Acidemia (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
For Parents and Patients
Propionic Acidemia (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources;
from the 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)
Clearinghouse for local, state, and national newborn screening education, programs, policies, and resources. Also, provides
many ways for people to connect and share their viewpoints and questions about newborn screening, supported by the U.S. Department
of Health and Human Services.
Center for Parent Information and Resources (DOE)
Parent Centers in every state provide training to parents of children with disabilities and provide information about special
education, transition to adulthood, health care, support groups, local conferences, and other federal, state, and local services.
See the "Find Your Parent Center Link" to find the parent center in your state.
Tools
ACT Sheet for Elevated C3-Acylcarnitine (ACMG) (
347 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) ( 194 KB)
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 (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.
Services for Patients & Families Nationwide (NW)
| Service Categories | # of providers* in: | NW | Partner states (4) (show) | | NM | NV | RI | UT | |
|---|---|---|---|---|---|---|---|---|---|
| Biochemical Genetics (Metabolics) | 1 | 1 | 2 | 3 | 2 | ||||
| Developmental Assessments | 1 | 105 | 5 | 35 | 54 | ||||
| Genetic Testing and Counseling | 6 | 6 | 12 | 8 | 11 | ||||
| Medical Genetics | 1 | 2 | 5 | 4 | 7 | ||||
| Newborn Screening Services | 1 | 3 | 2 | 2 | 3 | ||||
| Nutrition, Metabolic | 11 | 11 | 13 | 13 | 11 | ||||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Studies
Propionic Acidemia in Children (ClinicalTrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
Helpful Articles
PubMed search for propionic acidemia in infants, last 3 years
Forny P, Hörster F, Ballhausen D, Chakrapani A, Chapman KA, Dionisi-Vici C, Dixon M, Grünert SC, Grunewald S, Haliloglu G,
Hochuli M, Honzik T, Karall D, Martinelli D, Molema F, Sass JO, Scholl-Bürgi S, Tal G, Williams M, Huemer M, Baumgartner MR.
Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.
J Inherit Metab Dis.
2021;44(3):566-592.
PubMed abstract / Full Text
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.
Fraser JL, Venditti CP.
Methylmalonic and propionic acidemias: clinical management update.
Curr Opin Pediatr.
2016;28(6):682-693.
PubMed abstract / Full Text
Fraser JL, Venditti CP.
Methylmalonic and propionic acidemias: clinical management update.
Curr Opin Pediatr.
2016;28(6):682-693.
PubMed abstract / Full Text
Fraser JL, Venditti CP.
Methylmalonic and propionic acidemias: clinical management update.
Curr Opin Pediatr.
2016;28(6):682-693.
PubMed abstract / Full Text
Page Bibliography
Chapman KA, Gramer G, Viall S, Summar ML.
Incidence of maple syrup urine disease, propionic acidemia, and methylmalonic aciduria from newborn screening data.
Mol Genet Metab Rep.
2018;15:106-109.
PubMed abstract / Full Text
Forny P, Hörster F, Ballhausen D, Chakrapani A, Chapman KA, Dionisi-Vici C, Dixon M, Grünert SC, Grunewald S, Haliloglu G,
Hochuli M, Honzik T, Karall D, Martinelli D, Molema F, Sass JO, Scholl-Bürgi S, Tal G, Williams M, Huemer M, Baumgartner MR.
Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.
J Inherit Metab Dis.
2021;44(3):566-592.
PubMed abstract / Full Text
Fraser JL, Venditti CP.
Methylmalonic and propionic acidemias: clinical management update.
Curr Opin Pediatr.
2016;28(6):682-693.
PubMed abstract / Full Text
Pillai NR, Stroup BM, Poliner A, Rossetti L, Rawls B, Shayota BJ, Soler-Alfonso C, Tunuguntala HP, Goss J, Craigen W, Scaglia
F, Sutton VR, Himes RW, Burrage LC.
Liver transplantation in propionic and methylmalonic acidemia: A single center study with literature review.
Mol Genet Metab.
2019;128(4):431-443.
PubMed abstract / Full Text
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.