Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia

NCT02890342 | Recruiting

• 2 other identifiers: 16015616-HG-0156
• Study Type: observational
• Target: 1,045
• Locations: 1 country
• Sites: 2

Brief Summary

Background: People s bodies need to break down food into the chemicals. These chemicals are used for energy and growth. Some people cannot process all chemicals very well. Too much of some chemicals can cause diseases. One of these diseases is called propionic acidemia (PA). People with PA can have problems with growth, learning heart, abdomen, and other organs. Researchers want to better understand how these problems happen. Objective: To learn more about propionic acidemia and the genes that might contribute to it. Eligibility: People at least 2 years old with PA who can travel to the clinic Some unaffected family members Design: Participants will have a 3 to 5-day hospital visit every year or every few years. Family members may have just 1 visit. During the family member visit, they may have: Medical history Physical exam Samples of blood and urine Questions about diet and a food diary Doctors and nurses may do additional studies: Samples of saliva, skin and stool Fluid from a gastronomy tube, if participants have one Dental and eye evaluations A kidney test - a small amount of dye will be injected and blood will be collected. Consultations with specialists A test of calories needed at rest. A clear plastic tent is placed over the participant to measure breathing. Stable isotope study. Participants will take a nonradioactive substance then blow into a bag. Photos taken of the face and body with underwear on Ultrasound of the abdomen Heart tests Hand x-ray Brain scan Participants may have other tests if study doctors recommend them. They will get the results of standard medical tests and genetic tests.

Conditions

Metabolic Disease; Propionic Acidemia; Organic Acidemia

Keywords

Organic Acidemia; Inborn Errors of Metabolism; Natural History

Outcome Measures

Primary Outcomes (1)

• Natural history to asess long term complications of Propionic Acidemia

  assessing the long term complications of Propionic Acidemia during a week long evaluation with imaging, labs, and consultations.

  Ongoing

Study Arms (3)

Affected Patients with Propionic Acidemia

Patients with Propionic Acidemia, standard adult, parental permission

Healthy Volunteers

Healthy Volunteers, standard adult, parental permission

Unaffected Family Members

Unaffected family members

Eligibility Criteria

• Age: 1 Month - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Propionic Acidemia

You may qualify if:

• Patients 2 years of age or older, of any gender and ethnicity, with propionic acidemia are eligible to enroll in this protocol. Patients diagnosis will be confirmed based on biochemical and/or molecular and enzymatic testing. Participants of any gender and ethnicity over 1 month of age are eligible to enroll remotely for collection of outside records and natural history data. They will be eligible to enroll in the full study for in-person evaluation at 2 years of age.
• Unaffected family members over 1 month of age, of any ethnicity or race, may be included in the study as household controls for microbiome studies and/or for genetic analysis. Studies in unaffected family members may include collection of medical and family history; if necessary completion of physical examination; drawing of blood for research purposes include testing of DNA; collection of stool samples for microbiome studies; collection of dietary history using pen-and-paper or electronic food diary and questionnaires; collection of saliva for metabolite and DNA analysis. In some unaffected family members without a known familial cause of propionic acidemia, exome sequencing or genome sequencing could be performed. Unaffected family members will not receive direct benefit from taking part in the study.
• If a participant becomes pregnant while on study, the participant can remain on study. The only way to learn more about the critical biological differences in those who affected with propionic acidemia who are pregnant is to continue to follow pregnant women on study.
• However, no tests or procedures that are greater then minimal risk will be performed. Affected subjects who are pregnant may undergo procedures as part of their clinical care, including blood draws, genetic studies, and consultations, according to the clinical judgement of the clinical team. However, pregnant participants will be excluded from procedures such as organ tissue collection, stable isotope studies, GFR testing, and brain or cardiac MRI until the pregnancy is concluded.
• Healthy volunteers may be eligible to participate in the study if they are between 12 - 40 years of age, must meet specific BMI criteria (similar to affected individuals studied).
• Patients with propionic acidemia over 1 month of age, of any gender and ethnicity, undergoing a transplantation surgery at Children s Hospital of Pittsburgh, are eligible to participate in the tissue collection arm of the study.

You may not qualify if:

• A subset of participants may be enrolled in the tissue collection part of the study only (i.e. if they are too sick to travel). We can may also arrange limited remote consultation with our research team and NIH consultants, the participants referring physician and the participant/their legal guardian through the telephone or an NIH supported telehealth platform for participants who are unable to safely travel to NIH. This would not replace a study visit but would be used when travel isn t possible due to extenuating circumstances (e.g. pandemic). Participants would be encouraged to follow-up for a more thorough in-person evaluation when they are able to travel to NIH.
• For the healthy volunteers, they will be excluded if they have halitosis, cavities, dental or gingival problems, respiratory diseases (for example, asthma or recent history of COVID19), use tobacco products (for example, cigarette smoking or chewing tobacco), or use electronic nicotine delivery systems (for example, use of e-cigarettes or vaping devices), as this may interfere with accurate measurement of their volatile organic compounds. NIH staff and their family members will be eligible to participate in the healthy volunteer portion of the study.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Related Publications (3)

• Shchelochkov OA, Davies H, Mohney RP, Hatch A, Birch O, Ferry S, Van Ryzin C, Hall C, McCoy S, Vockley J, Kuo MJM, Manoli I, Sloan JL, Venditti CP. Breath biopsy in inborn errors of metabolism: A proof-of-principle study in propionic acidemia. Mol Genet Metab. 2025 Mar;144(3):109005. doi: 10.1016/j.ymgme.2024.109005. Epub 2024 Dec 21.

  PMID: 39787887 DERIVED

• Shchelochkov OA, Manoli I, Juneau P, Sloan JL, Ferry S, Myles J, Schoenfeld M, Pass A, McCoy S, Van Ryzin C, Wenger O, Levin M, Zein W, Huryn L, Snow J, Chlebowski C, Thurm A, Kopp JB, Chen KY, Venditti CP. Severity modeling of propionic acidemia using clinical and laboratory biomarkers. Genet Med. 2021 Aug;23(8):1534-1542. doi: 10.1038/s41436-021-01173-2. Epub 2021 May 18.

  PMID: 34007002 DERIVED

• Shchelochkov OA, Manoli I, Sloan JL, Ferry S, Pass A, Van Ryzin C, Myles J, Schoenfeld M, McGuire P, Rosing DR, Levin MD, Kopp JB, Venditti CP. Chronic kidney disease in propionic acidemia. Genet Med. 2019 Dec;21(12):2830-2835. doi: 10.1038/s41436-019-0593-z. Epub 2019 Jun 28.

  PMID: 31249402 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Metabolic Diseases; Propionic Acidemia; Metabolism, Inborn Errors

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Amino Acid Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Charles P Venditti, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susan C Ferry, R.N.

CONTACT

(301) 496-6213; pastudy@mail.nih.gov

Charles P Venditti, M.D.

CONTACT

(301) 496-6213; venditti@mail.nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2016
• First Posted: September 7, 2016
• Study Start: November 29, 2016
• Primary Completion (Estimated): August 31, 2036
• Study Completion (Estimated): August 31, 2036
• Last Updated: April 20, 2026

Record last verified: 2025-09-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)