I don't believe failure to be "in pursuance of the original constitution" can render an amendment unconstitutional.
Amendments serve to permit the constitution to be modified - not just the wording, but the spirit. That's why there's such a large consensus required to ratify an amendment - there is no provision to restrict what an amendment can do.
This is perfectly intentional - the good judgement of the citizens of the United States should make it hard to pass an amendment, and the constitutional authors didn't believe their own judgment to be superior, for all time, than the judgment of the people living in that time.
So, to answer your question fully, not being in pursuance of the original constitution is in no way a detriment for an amendment - in fact, any amendment that's solely in pursuance of the original constitution is probably unneccessary.
Edit:
In light of your revision, Asker, I belive that you disagree with all major constitutional scholars on the meaning of "in Pursuance thereof." I haven't encountered a view elsewhere that claims the Constitution as written was intended to be impossible to change, even in spirit. On the contrary, one of the often-referenced strengths of the document is that it makes radical change possible - even to itself - without reqiring that the govenment be overthrown by force.
While I can see where your interpretation comes from, I believe you've made an error, elevating the original state of the constitution above the process it provides for its own amendment.
The constitution specifically says, "The Congress, whenever two thirds of both Houses shall deem it necessary, shall propose Amendments to this Constitution, or, on the Application of the Legislatures of two thirds of the several States, shall call a Convention for proposing Amendments, which, in either Case, shall be valid to all Intents and Purposes, as Part of this Constitution, when ratified by the Legislatures of three fourths of the several States, or by Conventions in three fourths thereof, as the one or the other Mode of Ratification may be proposed by the Congress; Provided that no Amendment which may be made prior to the Year One thousand eight hundred and eight shall in any Manner affect the first and fourth Clauses
An amendment, duly approved by congress and ratified by the various states, by definition, cannot be unconstitutional. That is the whole point of amendments.