There is no issue upgrading the software from X12.5 directly to X12.6.4 - no intermediate steps are involved for this (but may be for other upgrades - see the Release Notes for any special requirements).
The only "issues" you may have will be related to any functionality changes. These are also documented in the Release Notes. It's always recommended that you consult these and determine if there is anything contained within them that may affect your particular deployment.
Wayne -- Please remember to mark helpful responses and to set your question as answered if appropriate.