Thanks for your comment, nandixon. I particularly appreciate the correction on the ammonia elimination and have edited my posts accordingly.
I looked at the raw data on 23andme and it says I have 38 SNPs. That's 38 out of 42. I read somewhere that single CAT GCH1 mutations lead to 30-70% reductions in BH4 levels. So I think it's safe to assume that I'm at least 30% impaired.
I think you understand now that everyone who tested with 23andMe on the v3 platform will have 38 SNPs listed. What relevance each has depends on whether a particular SNP has any effect at all (many don't) on either the function of the enzyme or transcription of the gene (among other possibilities), and on whether you are heterozygous or homozygous for the SNP.
Note that, by definition, a SNP does not cause disease, because these are simply variations, albeit some of them pretty rare. Some SNPs can definitely predispose to disease (or to good health), but other factors will be required for the disease to manifest itself (e.g., combinations with other SNPs and/or environmental exposures and/or epigenetic effects, etc.).
On the other hand, a true mutation might very well cause disease. 23andMe mostly does not test for these. For example, on the GCH1 gene (which contains over 60,000 base pairs, I think), there are well over a hundred actual disease-causing mutations.
According to SNPedia, gs224 reduces median plasma BH4 levels by approximately 80%. If that's what you have, I would expect BH4 to be very helpful for you. Here is why:
The study cited measured BH4 only in patients suffering from coronary artery disease (CAD). Healthy controls were used for alleleic frequency determinations only.
The 80% reduction doesn't appear to apply to either healthy people or to people suffering from ME/CFS. A number of us with the "gs224" haplotype had our biopterin levels measured and they were perfectly normal. We also tried BH4 supplementation and it wasn't helpful (e.g., I tried 2.5mg to 25mg with no effect). It might be helpful for someone else though, of course.
(I think the person who wrote the SNPedia blurb may be the moderator of the Yahoo gs224 group, so I'll ask her to place a big caveat with the 80% citation.)
Recent research shows that BH2 can be rescued by DHFR as well as by DHFRL1. So even if all of your supplemental BH4 was oxidized, your body has at least two pathways to salvage it.
The problem is that the higher the amount of BH2 becomes - relative to BH4 - the more that decoupling of eNOS occurs, which in turn causes more oxidation of BH4 to BH2, and a vicious cycle ensues. (This is from the 2009 and subsequent work of Crabtree.)
Regarding those ratios, if taking Kuvan did not raise BH4, then Kuvan wouldn't work for PKU. You need BH4 to break down phenylalanine. Without it, you die.
If I remember correctly, it actually tends to be very hit or miss in its effectiveness here, surprisingly.
My MTHFR mutation is C677T and I usually take a large L-5MTHF supplement. However, L-5MTHF doesn't give me nearly the boost that BH4 does. There are experiments that incorporated both BH4 and L-5MTHF that had excellent results. The challenge is scavenging peroxynitrite - taking Kuvan doesn't seem to lower peroxynitrite levels on its own. I suspect you need agmatine, arginine or other antioxidants to really make a dent. I personally take s-acetyl glutathione, Vitamin C, Gamma E tocopherals and inosine which have all be shown to do so.
I'm pretty sure that the most effective peroxynitrite scavenger, specifically with respect to maintaining BH4 levels, is methylfolate.
I heard from the owner that BH4 sales have been very strong for Spectrum Supplements, far beyond expectations. I don't think the parents of ASD kids would keep spending the money if BH4 wasn't helping. Recent studies show great promise for mental illnesses without all the nasty side effects. I look forward to seeing BH4 treat a host of neurological diseases as well as metabolic disorders, cardiovascular disease, and with luck, ME/CFS.
A lot of those parents are desperate for anything that helps, but it'll be interesting to see how BH4 plays out in autism.