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It is interesting to consider that there are catalytic domain HCU mutations that result in a CBS enzyme with normal basal activity but non-responsive to SAM 41

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In personal communication with the authors, they state the relief of symptoms is due to lowering of pressure on the venous system suggesting that venous disease is important in the diagnosis of lipohypertrophy

Finally, while rodent models demonstrate compelling proof-of-concept (e.g., SCFA supplementation ameliorates OA), the translatability of these findings to human physiology, with its greater complexity and longer disease course, is a significant hurdle that future research must overcome (30)