Clinical Trial: Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: The Natural History, Physiology, Microbiome and Biochemistry Studies of Propionic Acidemia

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

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 cou
Sponsor: National Human Genome Research Institute (NHGRI)

Current Primary Outcome: The study is non-interventional, prospective [ Time Frame: Study Completion ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: September 3, 2016
Date Started: July 28, 2016
Date Completion: August 1, 2030
Last Updated: April 21, 2017
Last Verified: February 16, 2017