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When metabolic encephalopathy is clearly documented with its underlying cause , it signals greater clinical complexity and can move the case into a higher-weighted DRG

49,54 In addition, the large size of mRNA and its susceptibility to degradation by nucleases result in low cellular uptake, further limiting its application

While some endocrine abnormalities (e.g., hypothalamicpituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment