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Deficiencies in CBS activity caused by genetic mutations of the CBS gene are the most frequent cause of familial HHCy.121 There are at least 153 mutations known to exist in the CBS gene, with several significantly reducing CBS activity.121 These genetic CBS deficiencies can be divided into two major allelic variance types: vitamin B 6 responsive and vitamin B 6 nonresponsive.122,123 Individuals with some of these genetic variants are likely to have both decreased production of H 2 S and elevated levels of HCy