Patient case (clinical description): A 51-year-old man comes to the office complaining of fatigue and some sexual problems including lack of libido. The patient doesn't smoke or use any illicit drug.  Blood pressure is 120/80 mm Hg and pulse is 70/min.  Oxygen saturation is 99% on room air.  BMI is 24 kg/m2.  Skin examination shows increased pigmentation. Genotype testing is consistent with homozygosity for the C282Y mutation. Laboratory study shows transferrin saturation of 55% and serum ferritin of 550 μg/L. He is diagnosed as a case of hemochromatosis.

Patient's own account: I am 51 years old and I just came back from the doctor's office. I'm sick and tired of being that exhausted, reaching the point where me and my lovely wife are not touching each other anymore! I'm not smoking or doing drugs! My blood pressure was 120/80 mm Hg, and pulse was 70/min and my oxygen saturation 99%. My BMI is 24. My skin also turned a bit darker lately. He tested my genes and told me that I have a mutation of the C282Y gene. I also did lab tests where my transferrin saturation was 55% and serum ferritin was 550  μg/L. The doctor diagnosed me with iron overload.

Clinical trial: Cardiac Function in Patients With Hereditary Hemochromatosis

Eligibility criteria:
-  INCLUSION CRITERIA:

        HH Patients

        Group A patients (untreated HH patients)

        Adults 21 years or older

        New York Heart Association Functional Classification Class I

        Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum
        ferritin level above 400 ng/ml or documented % iron saturation more than 60%.

        Patient has not received standard chronic phlebotomy or deferoxamine treatment. Individuals
        are allowed to have up to 3 emergency phlebotomies for alleviation of severe iron
        accumulation before enrollment.

        Group B patients (treated HH patients)

        Adults 21 years or older

        New York Heart Association Functional Classification Class I

        Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum
        ferritin level above 400 ng/ml or documented % iron saturation more than 60%.

        Patient has been compliant with standard phlebotomy and/or deferoxamine treatment for 6
        months or longer and in stable phase with iron saturation 50% or less.

        Healthy Volunteers

        Group C Patients (Age-Gender Matched Healthy Control Subjects)

        Adults 21 years or older.

        No symptoms suggestive of heart disease or any other medical conditions, negative Hfe
        genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation.

        EXCLUSION CRITERIA:

        HH patients

        Group A patients (untreated HH patients)

        Pregnant or lactating women

        History or present evidence of coronary artery disease, heart failure, peripheral vascular
        disease, coagulopathy, or uncontrolled hypertension (systolic blood pressure over 170 mmHg
        and/or diastolic pressure over 100 mmHg).

        History of significant end-organ damage secondary to HH.

        Serum creatinine greater than 2.0 mg/ml

        LFT's more than 2.5 times above upper limit of normal

        History of structural cardiac disease except mitral valve prolapse with mild mitral
        regurgitation

        Uncontrolled glucose levels with hemoglobin A(1c) above 8 mg/dl or the use of more than one
        oral hyperglycemic agents or insulin therapy to control diabetes.

        Current use of antioxidant treatment such as vitamin E and C. However, the cessation of
        this treatment 4 weeks prior to the study will allow for inclusion.

        Evidence of impaired immunity including HIV

        Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular
        disease.

        Participation in unrelated research involving investigational pharmacological agent in past
        30 days.

        Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.

        Inability to provide informed consent

        Smoking in past 3 months.

        Use of beta-adrenergic blocking agents and calcium channel blockers with negative
        chronotropic effect within 1 week.

        Inability to perform treadmill or bicycle exercise testing.

        Inability to undergo MRI such as ferromagnetic implant.

        Group B patients (treated HH patients)

        Pregnant or lactating women

        History or present evidence of coronary artery disease, heart failure, peripheral vascular
        disease, coagulopathy, or uncontrolled hypertension (systolic blood pressure over 170 mmHg
        and/or diastolic pressure over 100 mmHg).

        History of significant end-organ damage secondary to HH.

        Serum creatinine greater than 2.0 mg/ml

        LFT's more than 2.5 times above upper limit of normal

        History of structural cardiac disease except mitral valve prolapse with mild mitral
        regurgitation

        Uncontrolled glucose levels with hemoglobin A(1c) above 8 mg/dl or the use of more than one
        oral hyperglycemic agents or insulin therapy to control diabetes.

        Current use of antioxidant treatment such as vitamin E and C. However, the cessation of
        this treatment 4 weeks prior to the study will allow for inclusion.

        Evidence of impaired immunity including HIV

        Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular
        disease.

        Participation in unrelated research involving investigational pharmacological agent in past
        30 days.

        Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.

        Inability to provide informed consent

        Smoking in past 3 months.

        Use of beta-adrenergic blocking agents and calcium channel blockers with negative
        chronotropic effect within 1 week.

        Inability to perform treadmill or bicycle exercise testing.

        Inability to undergo MRI such as ferromagnetic implant.

        Healthy volunteers

        Group C Patients (Age-Gender Matched Healthy Control Subjects)

        Pregnant or lactating women.

        History or present evidence of any structural cardiac disease except mitral valve prolapse
        with mild mitral regurgitation, heart failure, peripheral vascular disease, coagulopathy,
        and uncontrolled hypertension (systolic blood pressure over 170 mmHg and/or diastolic
        pressure over 100 mmHg).

        Serum creatinine greater than 2.0 mg/ml.

        LFT's more than 2.5 times above upper limit of normal.

        Current use of antioxidant treatment such as vitamin E and C. However, the cessation of
        this treatment 4 weeks prior to the study will be included.

        Uncontrolled glucose levels with hemoglobin A(1C) above 8 mg/dl or the use of oral
        hyperglycemic agents or insulin therapy to control diabetes.

        Evidence of impaired immunity including HIV.

        Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular
        disease.

        Participation in unrelated research involving investigational pharmacological agent in past
        30 days.

        Current alcohol use (more than 26 grams averaged ethanol intake per day) or drug abuse.

        Inability to provide informed consent.

        Smoking in past 3 months.

        Subjects with any chronic medical problems*

        Inability to undergo MRI such as ferromagnetic implant.

        *For the purpose of this protocol "chronic medical problems' is defined as any current
        condition not amenable to curative therapy and which requires long-term medical treatment
        and/or clinical monitoring.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 21 Years old.


Eligibility (NLI label): Entailment