Oxidative Stress Markers In Inherited Homocystinuria And The Impact Of Taurine

Inclusion Criteria:

1. A confirmed biochemical, molecular, or enzymatic diagnosis of classic homocystinuria
due to cystathionine beta-synthase deficiency (OMIM 236200)

2. And not fully responsive to therapy (eg, total homocysteine (tHcy) levels above 50
µmol/L on therapy including on B6 therapy)

3. Be over 8 years old and less than 50 years. The first four patients will be adults
(age 18-50 years)

4. Be able and willing to provide informed consent

Exclusion Criteria:

1. Age less than 8 years: Individuals under 8 years of age will be excluded due to blood
volume issues and concerns regarding their ability to assent

2. Age greater than 50 years: Individuals over 50 years will be excluded due to possible
age related differences in markers of oxidative stress and inflammation

3. Pregnancy: Females who are pregnant or lactating will be excluded from the study as
the influence of pregnancy on the markers is not known nor is the safety of taurine
supplementation in pregnancy.

4. Continued antioxidant intake:

1. Individuals currently taking taurine, over the counter energy drinks containing
taurine or other high dose antioxidants and unwilling to discontinue this for
the study period (including a 2 week wash out period) will be excluded as such
intake will likely impact laboratory results.

2. Individuals taking Vitamin C as a prescribed treatment for their homocystinuria
will be excluded as the antioxidant therapy may impact antioxidant and
inflammation markers. (As Vitamin C is not standard of care for this disease we
anticipate this to have minimal impact on recruitment.)

3. Individuals currently taking platelet aggregation inhibitors such as salicylate
on a self prescribed basis and unwilling to discontinue this for the study
period (including a washout period of at least two weeks prior to the study)
will be excluded as salicylate intake will impact platelet study results.
Individuals taking salicylate (or other platelet aggregation inhibitors)
prescribed as a therapy for their homocystinuria or other health issues will not
be asked to stop the medication. They will participate in the study, but will be
excluded only from the platelet studies.

5. Medication interactions: Individuals unable or unwilling to abstain from use of
cyclic guanosine monophosphate (cGMP) phosphodiesterase 5 inhibitors (such as Viagra)
during the study period will be excluded from the nitroglycerin-induced flow-mediated
dilatation studies in accordance with known labeling contraindications.

6. Inflammatory status:

1. Individuals who have a significant chronic illness that has a marked
inflammatory component will be excluded from the study as the illness will
impact inflammatory markers.

2. Patients with an acute illness, which may impact inflammatory biomarkers, will
be postponed for study entry until the acute illness is resolved. Entry into the
study at a later day will be offered.

7. Recent cardiovascular event. Cardiovascular events (stroke, myocardial infarct, deep
vein thrombosis, pulmonary embolus, thrombosis, or uncontrolled hypertension) may
interfere with platelet function studies and with various mediators during the first
months after the event. Patients who had such an event within the last 6 months will
be excluded.

8. Hypertriglyceridemia. Individuals with a triglyceride level above 300 mg/dl will be
excluded from the study.

9. Informed consent: Individuals who are unwilling or unable to consent, or in the case
of minors who are unwilling or unable to assent will be excluded due to lack of
ability to ensure informed consent.

10. Study compliance and integrity: Individual who anticipate an inability to comply with
study procedures and requirements will be excluded.

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