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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02890342
Recruitment Status : Recruiting
First Posted : September 7, 2016
Last Update Posted : September 25, 2018
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

September 3, 2016
September 7, 2016
September 25, 2018
September 3, 2016
August 1, 2036   (Final data collection date for primary outcome measure)
Natural history to asess long term complications of Propionic Acidemia [ Time Frame: Study Completion ]
assessing the long term complications of Propionic Acidemia during a week long evaluation with imaging, labs, and consultations.
The study is non-interventional, prospective [ Time Frame: Study Completion ]
Complete list of historical versions of study NCT02890342 on Archive Site
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Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia
The Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia


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.


To learn more about propionic acidemia and the genes that might contribute to it.


People at least 2 years old with PA who can travel to the clinic

Some unaffected family members


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.

Propionic acidemia (PA) is one of the most common inborn errors of organic acid metabolism. Although this disorder is now routinely detected in the immediate neonatal period on the US newborn screen, clinical outcomes are poor despite timely and aggressive medical intervention [Kolker, Cazorla, et al 2015; Leonard et al 2003]. Worldwide, the incidence of PA varies widely. The estimated live-birth incidence of PA is 1:105,000-130,000 in the US [Chace et al 2001; Couce et al 2011], 1:166,000 in Italy [Dionisi-Vici et al 2002] and 1:250,000 in Germany [Schulze et al 2003]. Affected patients are medically fragile and can suffer from complications such as failure to thrive, intellectual disability, basal ganglia strokes, seizures, cardiomyopathy, cardiac arrhythmias, pancreatitis, impaired gut motility, and hematological complications. The frequency of these complications in the US patients and their precipitants remain undefined. Furthermore, current treatment outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Specific treatments include dietary modification to reduce propiogenic precursor load, levocarnitine to facilitate excretion of propionate, and oral antibiotics to suppress propiogenic gut flora. More recently, solid organ transplantation (liver and/or kidney) has been used to treat PA patients. However, optimal transplant strategy and posttransplant

management are incompletely understood.

Several survey-based and retrospective studies describing the natural history of propionic acidemia have been published in the last decade [Baumgartner et al 2014; Kolker, Cazorla, et al 2015; Kolker, Valayannopoulos, et al 2015; Kraus et al 2012; Nizon et al 2013; Pena & Burton 2012; Pena, Franks, et al 2012]. While these publications added to our understanding of the clinical course of this disease, the studies have not systematically focused on the US population using prospective analysis and reflect largely European experience, where many developed countries do not routinely screen for PA using newborn screen. Thus, the benefits of newborn

screening on the PA outcomes require further clarification [Grunert et al 2012].

Under proposed NIH protocol, we will prospectively evaluate patients with propionic acidemia with special emphasis on the US population. Routine inpatient admissions and outpatient evaluations will last 4-5 days and involve blood drawing, urine collection, stool collections, genomic studies, ophthalmological examination, cardiology evaluation, radiological procedures, brain and cardiac MRI/MRS, dietary assessment and neurobehavioral evaluation. In some patients skin biopsies will be pursued.

The study objectives will be to describe the natural history of propionic acidemia in the US patients by delineating the spectrum of phenotypes and querying for genotype, enzymology, microbiome, and phenotype correlations. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from, Organic Acidemia Association and Propionic Acidemia Foundation. Patients will be evaluated at the NIH Clinical Center. Outcome measures will largely be descriptive and encompass correlations between clinical, microbiological, biochemical and molecular parameters.

Observational Model: Cohort
Time Perspective: Prospective
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Non-Probability Sample
Patients with Propionic Acidemia
Metabolic Disease
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Propiomic Academia
Patients with Propionic Acidemia and their family members.
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
August 1, 2036
August 1, 2036   (Final data collection date for primary outcome measure)
  • Patients 2 years of age and older are eligible to enroll in this study.
  • Patients with biochemical, molecular or enzymatic evidence of propionic acidemia of any gender and ethnicity are eligible to enroll in this protocol.
  • Patients with suspected genetic but unknown types of propionic acidemia may also be invited to participate.


  • Patients will be excluded if they cannot travel to the NIH because of their medical condition.
  • Pregnant patients are eligible to participate in the study. However, they may not take part in some tests, for example stable isotope studies.
  • The principal investigator may decline to enroll a patient for other reasons. Other criteria that may lead to exclusion include, for example, residing in a hospital, suboptimal metabolic control as determined by Dr. Venditti's review of the laboratory data, any patient who requires dialysis once or more in a week and weighs less than 40 kg, any patient who is being treated for an intercurrent infection with antibiotics or has evidence of an acute infection, and any patient who does not have a regular/local metabolic, genetic or endocrine physician and/or a family physician, pediatrician, or internist.
Sexes Eligible for Study: All
2 Years to 100 Years   (Child, Adult, Older Adult)
Contact: Charles P Venditti, M.D. (301) 496-6213
United States
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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
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National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
National Human Genome Research Institute (NHGRI)
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Principal Investigator: Charles P Venditti, M.D. National Human Genome Research Institute (NHGRI)
National Institutes of Health Clinical Center (CC)
September 20, 2018