Homocystinuria: Treatment With N-Acetylcysteine

Homocystinuria (MIM 236200) due to CBS deficiency is the most common inborn error of sulfur amino acid metabolism with severe clinical manifestations. We propose:

• An open-label pilot study of N-acetylcysteine (NAC) to lower plasma homocysteine levels in those that have not responded to conventional treatment which includes betaine (Cystadane®, Orphan Medical Inc.), which while lowering Hcy levels does not normalize it, and is very expensive. There are no known contraindications to NAC used for nutritional supplementation and it is relatively inexpensive.

Oral NAC has reduced total plasma homocysteine in healthy subjects in a dose-dependent fashion.

• Measurement of flow-mediated vasodilation of the brachial artery (endothelial function) in response to NAC treatment. Endothelial dysfunction is a precursor of atherogenesis.
• Sequencing the CBS gene in these individuals in order to identify novel mutations causing homocystinuria and identify polymorphisms in other genes that may affect response to treatment.

Inclusion criteria

• Homocystinuria (lens dislocation and hyperhomocysteinemia)
• Age ≥ 18 (the age of majority in Canada)

Exclusion criteria

• Nursing mothers or pregnant women
• Chronic liver disease
• Taking nitrates
• Cystine stone formers
• History of active peptic ulcer disease
• Subjects receiving carbamazepine and metoclopramide
• Use of other products containing cysteine or N-acetylcysteine (e.g. nebulized NAC, cysteine supplements, methionine restriction)
• Hypersensitivity to any ingredient in the study product
• Clinically significant, abnormal laboratory test on screening (Visit 2)

Other Criteria:

• Women of child-bearing capacity must be using an acceptable method of birth control and have a negative pregnancy test before being enrolled