You'll want to think about the lattice of subsets of the letters, ordered by inclusion. Essentially, you have a value f(S) given for every subset S of size 2 (that is, every off-diagonal element of the matrix - the diagonal elements don't seem to occur in your problem), and the problem is to find, for each subset T of size greater than two, the minimum f(S) over all S of size 2 contained in T. (And then you're interested only in sets T that contain a certain element "A" - but we'll disregard that for the moment.)
First of all, note that if you have n letters, that this amounts to asking Omega(2^n) questions, roughly one for each subset. (Excluding the zero- and one-element subsets and those that don't include "A" saves you n + 1 sets and a factor of two, respectively, which is allowed for big Omega.) So if you want to store all these answers for even moderately large n, you'll need a lot of memory. If n is large in your applications, it might be best to store some collection of pre-computed data and do some computation whenever you need a particular data point; I haven't thought about what would work best, but for example computing data only for a binary tree contained in the lattice would not necessarily help you anything beyond precomputing nothing at all.
With these things out of the way, let's assume you actually want all the answers computed and stored in memory. You'll want to compute these "layer by layer", that is, starting with the three-element subsets (since the two-element subsets are already given by your matrix), then four-element, then five-element, etc. This way, for a given subset S, when we're computing f(S) we will already have computed all f(T) for T strictly contained in S. There are several ways that you can make use of this, but I think the easiest might be to use two such subset S: let t1 and t2 be two different elements of T that you may select however you like; let S be the subset of T that you get when you remove t1 and t2. Write S1 for S plus t1 and write S2 for S plus t2. Now every pair of letters contained in T is either fully contained in S1, or it is fully contained in S2, or it is {t1, t2}. Look up f(S1) and f(S2) in your previously computed values, then look up f({t1, t2}) directly in the matrix, and store f(T) = the minimum of these 3 numbers.
If you never select "A" for t1 or t2, then indeed you can compute everything you're interested in while not computing f for any sets T that don't contain "A". (This is possible because the steps outlined above are only interesting whenever T contains at least three elements.) Good! This leaves just one question - how to store the computed values f(T). What I would do is use a 2^(n-1)-sized array; represent each subset-of-your-alphabet-that-includes-"A" by the (n-1) bit number where the ith bit is 1 whenever the (i+1)th letter is in that set (so 0010110, which has bits 2, 4, and 5 set, represents the subset {"A", "C", "D", "F"} out of the alphabet "A" .. "H" - note I'm counting bits starting at 0 from the right, and letters starting at "A" = 0). This way, you can actually iterate through the sets in numerical order and don't need to think about how to iterate through all k-element subsets of an n-element set. (You do need to include a special case for when the set under consideration has 0 or 1 element, in which case you'll want to do nothing, or 2 elements, in which case you just copy the value from the matrix.)
