Uric Acid Level Normal and Possible Rheumatoid Arthritis!

So I'm homozygous for the Q141K mutation in the ABCG2 gene, but a lab measured my uric acid to be 4.6 mg/dL.  This is a great reading for anyone struggling with gout.  The part I'm not so excited about is that more joints seem to be affected with arthritis since my onset in 2014 in spite of the normal uric acid level.  That begs the question as to how to stop the disease progression if I still have issues with normal uric acid levels. 

There could be more to the story.  My doctor says that the low white blood cell count could indicate a possible autoimmune disease and the multiple joint involvement could indicate rheumatoid arthritis.  She said this before I found out that I had a normal uric acid level.  So when I found out that the uric acid level was normal, I immediately began to worry that I really have rheumatoid arthritis.  My gout attack in 2014 seemed to be unique to gout as well as the flares related to eating foods high in purines.  But I'm not going to blow off the possibility that it could be RA.  It is also possible that I have both gout and RA.  The doctor had the lab draw more blood to check for indications of autoimmune disease.  I'll know the results within the next week or two.  I feel like I could be waiting to receive my "death sentence".  Autoimmune diseases are terrible to have from what I hear.  Having one is like having enduring a long painful death.  I also would have to be on medication to slow the disease progression.  By the way, I liked the doctor.

Pre-Doctor's Appointment Fussing

Typically I try to avoid fussing, but since it is not an uncommon occurrence for people suffering with "hard to see" illnesses to struggle with people not believing them I am fussing now.  I specifically requested a uric acid test before getting blood drawn last week.  However, there were no uric acid results in the lab results I looked at yesterday.  I'm miffed.  Perhaps she wanted to do a general physical first, but the whole point of seeing the doctor was to get an accurate measurement of my uric acid level.  I suspect she blew off my concerns and did not order the uric acid test.  I  know I'm not the typical gout patient, but I'm not imagining my joint pain.  There are not a whole lot of diseases that can be confused with gout.  This very morning, I had sharp pain in my right hip area and it hurt when I sat a certain way.  As usual, there is tingling in my big toe.  Perhaps she'll only order the uric acid test after my appointment today, the online platform only shows some lab results, she blew me off, or some other reason.  We'll see this afternoon! 

My labs did not show anything too odd, except perhaps, a low white blood cell count.  I really want that uric acid level measured because that would determine how aggressively I need to control it with diet and if my only hope of not being disabled in the near future is to be on pharmaceuticals.  If I understand it correctly, a uric acid level above 7 mg/dL is high.  6-7 mg/dL is not that great and people can still develop tophaceous gout.  Some people can develop chronic tophaceous gout with 5-6 mg/dL.  If my level is 7-8 mg/dl, I may have a chance at controlling it with diet alone.  If it is higher than 8 mg/dL I probably have to be on pharmaceuticals in order to halt the progression. 

If my doctor really did blow me off, I may need to purchase a more expensive home uric acid monitor.  There is one that measures uric acid, cholesterol, and glucose.  The components may be available to pickup in my area so the odds of the test strips being defective may be reduced.  I would not have to worry about shipping damaging the test strips.

On a practical note, it would help with planning to know approximately how long I have until I am struggling with the debilitating stage of the disease.  It is my goal to start a home based business and grow my family simultaneously.  There are a lot of businesses I probably should not be involved in due to the disease.

I already struggle with the following activities:

Standing for more than a few hours per day - My right hip gets sore, I start limping, and sometimes get sharp pain.  If I do a lot of standing my left hip starts hurting.  One time I got all around joint pain from standing all day, even in my fingers and elbows.  Other times I take a step and my right hip gives out.

Working with my hands - My right thumb starts throbbing and gets so stiff I cannot bend it all the way.  One time it was hard to pick up my baby.

There goes the idea of processing a lot of produce to make value added products to sell.  There goes the idea of selling crafts on Etsy.  There goes the idea of getting a part time job that requires a lot of standing.  I'm really only fit for desk work.  I was once a civil engineer in training, which is a desk job.  Perhaps I need to pass the Professional Engineering exam and get that license since is one of the few jobs I could still do now.

Gout Progression Update: Blood work

Hopefully my story could be used to further research on gout.  So again, I'll provide an update about the progression of my gout case.  I could not obtain a uric acid meter that accurately measured the uric acid level in my blood, so I decided to go to a doctor to get checked out.  So far, all I did was get my blood drawn.  My doctor thought it prudent to check my uric acid level, blood counts, and liver and kidney function.  We'll see what she found soon!  I'm guessing she's checking for any indications for an autoimmune disease and seeing if my kidneys are performing as they should be and other things doctors know to check for.  I checked all I had data for on the ABCG2 gene.  So far, it looks like I'm homozygous for the Q141K mutation.  I would not have thought my fingers, thumbs, hips, and toes would be affected by arthritis at such a young age.  I wonder if there's some undetectable deletion on the ABCG2 gene.  I may never know, but I'm curious what that uric acid level is.

Chromosome 6: Rare and Uncommon Variants

In Chromosome 6, I found a few uncommon variants, one of which affects the ability to tolerate allopurinol, which is used to treat gout.

rs3095318: MAF, A = 0.1018, risk allele, CDSN, PSORS1C1.
According to SNPedia, the variant is associated with HLA-B*5801 allele and allopurinol side effects in Japanese population.  

rs28381349: MAF, T = 0.0325, MSH5.  rs28381349 and rs1802127, MAF, C = 0.0289 (rs28399984) alleles always found together in Swedish patients with IG A deficiency and common variable immunodeficiency (CVID) but may not have complete penetrance.

rs3798220: MAF, C = 0.0513, LPA.  Associated with coronary artery disease.

rs7750641: MAF, C = 0.0238, TCF19.  It's a missense mutation so it may be important.

rs7741100: MAF, A = 0.0423.  

rs35445101: MAF, A = 0.0739.  Could be associated with hepatocellular carcinoma.

rs130060: MAF, C = 0.0034, HTR1B. 

rs2235197: MAF, A = 0.1104, UNC93A, stop gained.

rs17136358: MAF, C = 0.0607, EIF2AK1

Odds of Developing Gout About 19x Normal Rate

According to one study, the odds of my developing gout before my 30th birthday were about 19 times the normal rate.  My ABCG2 protein is about half functioning since I'm homozygous in the loss of function mutation Q141K.  Talk about the odds not being in my favor!  There is also the complete loss of function mutation, Q126K, that I'm thankfully not a recipient of.  Here's a handy chart showing that no to half functioning ABCG2 increases the odds of developing gout in one's lifetime.  Early onset gout, before the age of 30, is associated with mild to severe ABCG2 function.

Having no to only half function of the ABCG2 protein account for about 33% of all gout cases according to another study.  Most people with gout have some loss of ABCG2 function, about 75% of normal, or due to non-ABCG2 function factors (lifestyle choices perhaps?).   Here's another handy chart showing that no to half function in ABCG2 accounts for about a third of all gout patients.  Note that the odds for having normal uric acid levels, below 7 mg/dL for men, is slim to almost none for these patients.

One rheumatologist blew me off since it's unusual for women to develop gout so young, but she may not have been familiar with the genetic factor for developing gout.  Estrogen seems to upregulate ABCG2 function so women are generally not susceptible for developing gout before menopause.  So I cannot blame the rheumatologist.  Most gout patients, after all, have most or all of their ABCG2 function.  Many may have been overindulging in alcohol, purine rich foods, and even enjoying HFCS beverages quite a bit.  Many times its due to aging and the kidneys not functioning as well as they used to.  The ABCG2 protein is currently being studied so doctors may not be very familiar with it right now.

It helps to be more aware of the genetic factor however.  Looking at the charts my daughter is still more susceptible for gout than the average person with her ABCG2 being 75% functioning.  It's probably wise for her not to get on protein rich diets and not take whey protein on a regular basis if she wants to remain gout free. 

Chromosomes 5: Rare and Uncommon Variants

Searching through Chromosome 5 I detected a few rare and uncommon variants that 23andme tests for.

rs6884762: RAD50 gene with a MAF, T, of 0.0094.  It is an intron variant and may not be a big deal.

rs13167812: UIMC1 Gene with MAF, A, of 0.0048.  It is a missense variant.  The gene interacts with BRCA1 according to GeneCards.  BRCA1 is the more infamous gene associated with breast cancer.

Chromosome 4: Rare and Uncommon SNPs

I found a few SNPs in Chromosome 4 that are interesting.  

rs358231 in the GBA3 gene.  Some people have the allele that results in a premature stop codon.  Premature stop codons result in a truncated protein.  As far as I know truncated proteins do not "do their job".  MAF (minor allele frequency),T, is 0.1084 so it is not very rare.

rs1799895.  This is a pathogenic missense allele in the SOD3 gene where mutations can increases the risk of cerebral infarction in women, emphysema, and several other conditions according to GeneCards.  Fortunately, it is not the most common variant with a MAF, G, of 0.024.  This missense results in a codon that codes for the protein glycine instead of arginine.  It's rather unfortunate that my maternal grandmother died at the age of 43 of a cerebral infarction and I'm a recipient of the pathogenic allele.  My mother is alive and well in her late 50s.  Then again, there's my father that almost died of a brain hemorrhage, but he made it and is in his 60s. 

rs2231142.  This a missense mutation in the ABCG2 gene.  According to dbSNP, it is a "drug response allele" and also associated with gout.  The MAF, T, is 0.1194 so it is not very rare, but being homozygous reduces uric acid excretion by about 50%!  I have gout and am homozygous for this SNP and was not the most likely candidate for gout otherwise.

rs72552713.  This is the SNP that results in a premature stop codon in the ABCG2 protein.  MAF, T, is 0.0012.  Good thing I do not also have one of these SNPs!

rs2231134 with MAF, G =0.0124.  Upstream variant of the ABCG2 gene.  I'm not sure of the significance, but since I have gout, I'm watching out for more research on this and on rs2728125 (MAF, G = 0.099).  SNPs upstream of genes could potentially affect gene expression.  I'm heterozygous for the former and homozygous for the latter.

rs1281138 in SH3TC1 with MAF, A= 0.007.  I'm not sure of the function of this gene, but since it is a missense, I'm reporting on it.