Genetic and Environmental Determinants That Control Metabolism in Pulmonary Hypertension
Condition: Iron-sulfur Cluster Deficiency; Pulmonary Hypertension; Friedreich Ataxia
MeSH terms: Hypertension, Pulmonary; Friedreich Ataxia; Hypertension
Study type: Observational

Summary: 
      The investigators are performing this research study to determine whether having low
      iron-sulfur cluster levels can cause a disease known as pulmonary hypertension (PH). PH is
      defined as abnormally high blood pressure in the arteries of the lungs.

      Usually, small specialized structures inside each human cell called mitochondria are in
      charge of generating energy within lung arteries for normal function. During situations of
      disease or stress, lung arteries undergo a change in the function of mitochondria, resulting
      in the development of PH. In studies on mice, investigators have learned that alterations in
      the production of specific metal complexes called iron-sulfur clusters are responsible for
      these changes. This makes it more likely that mice will develop PH.

      In this study, the investigators want to find out if alteration of iron-sulfur cluster
      formation leads to increased likelihood of developing PH in humans.
    

Detailed description: 
      Test group:

      The study will include two visits for the test group:

      At visit one there will be required and optional research activities as the following:

      Required research activities:

      -Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to
      isolate PBMCs for generation of iPSCs.If patient did not want to give a blood sample we will
      ask if willing to give a urine sample. A clinical research coordinator will give the patient
      a plastic container and will explain how use it.

      The following research activities will be optional at visit one:

        1. Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron
           studies, and plasma for microRNA) processed at Presby Lab. This will be required if the
           patient approved to do right heart cath.

        2. Electrocardiogram.

        3. 6 Minute Walk Test.

        4. Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if
           patients agree to do, if not, we will only get a blood sample)

        5. Resting Echocardiogram

      This visit will last 7-8 hours.

      Study Visit Two:

      This will include optional Right Heart Catheterization.

        -  Right Heart catheterization by PI/Sub-Investigator. Duration ~ 3 hours

             -  IF the results show that the pressure in the lung vessels is elevated without
                exercise AND there is no other abnormality in the heart function, we will NOT do
                exercise testing.

             -  IF the patients are physically able to perform exercise testing/agree to do an
                exercise testing, patients will have an Exercise Right Heart catheterization and a
                Rest and Stress Echocardiography. (Determined by PI/Sub-Investigator

             -  All participants who will do right heart catheterization will have to do a
                pregnancy test before the procedure.

        -  Exercise Echocardiogram completed in. If patient unable to exercise medication
           (Dobutamine) will be given. Duration ~ 1-2 hours

        -  Exercise Right Heart catheterization Duration ~ 2-3 hours

      CONTROL GROUP

      Control group will only have one visit. At this visit there will be a minimum required
      research activity to participate in the study and this will include:

      -Peripheral blood draw (3.5 tablespoons) drawn by research coordinator. This blood is to
      isolate PBMCs for generation of iPSCs. If participant did not want to give a blood sample we
      will ask if willing to give a urine sample.

      The following research activists will be optional at visit one:

        1. Physical exam and blood work (kidney/liver, blood count, coagulation, B-HCG, iron
           studies, and plasma for microRNA) processed at Presby Lab. This will be required if the
           patient approved to do right heart cath.

        2. ECG, done by research coordinator and read by PI/Sub-Investigator.

        3. 6 Minute Walk Test, done by research coordinator, if patient could perform.

        4. Skin Biopsy from underarm or inner thigh by physician (Dermatology department) (if
           patients agree to do, if not, we will only get a blood sample) This visit will last 6-7
           hours.
    

Intervention name(s): Right Heart Catheterization; Blood draw
Intervention type(s): Procedure; Other
Intervention description(s): Some participants (i.e., those that are willing and able) will undergo a Right Heart Catheterization to check Cardiopulmonary function.; Test and control group will be asked to give 20 ml of blood samples
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population will include ten patients (ages 18-60 yrs) with confirmed mutations of
        the iron-sulfur cluster biogenesis complex of proteins. It will also include ten additional
        patients (ages 18-60 yrs) who are unaffected first-degree family members of the above
        subjects.
      
Biospecimen description: 
      We are generating inducible pluripotent stem cells from blood and skin biopsies from
      participants.