Gene Test for SLC40A1

Allergies, blood and immune system
1

Has anyone had the gene test for SLC40A1 for ferroportin disease? I convinced my doctor to order this but getting this approved through insurance seems tough in the U.S. Also im not sure which lab is best to have do this (ie cheapest) because if I wind up having to pay for it Id like to pick the cheapest one. The cheapest I found was Fulgent Labs in California which wants $1075 for the sequencing on this gene. Let me know if anyone has done this.

Generally your doctor sets this up but because of how rare this is, my gastro has not encountered this before and didn't have a recommendation.

2

I am not familiar with this...only the DNA test for HH, which i had in Colorado.....I hope you don't have to pay for it yourself...that's a lot of out of pocket expense. My test for HH was $900, and that was 2 years ago..Let us know how things turn out for you.

Leigh

3

Good morning,

Sorry, I am in the UK but, I have recently had gene test SLC40A1 for Ferroportin Disease for which I tested positive, I also am loading iron in my Liver which is currently 3 times the normal which was identified by a ferriscan, my ferritin levels were >5000 when diagnosed with Iron saturation of 21% - I know the test is expensive here in the UK too about £750, this was carried out at university hospital Oxford, the results took about 8 weeks to come through

Started Venesection last week every two weeks to see if the situation improves and if my Haemoglobin levels can cope with blood removal at this rate

Hope that you get that your test sorted and can move forward... Let us know how you progress

  

4

Hello hemopatient123

Yes I have, but I am in the UK and it was using the NHS.  I tested positive.  I hope you can find a solution to get a proper diagnosis.

Best wishes

Marie

5

Thanks Marie. The issue I am having is my doctor is suggesting this test is not medically necessary. He feels the treatment would be the sane regardless of the result as I am already a confirmed compound heterozygous for the HFE gene and on phlebotomy treatment. He wrote me a prescription for the SLC gene test but I will likely need to pay myself for it. Works a bit different here I guess

6

I have one copy of H63D and positive for SLC40A1.  My ferritin was circa 5000 and my transferrin saturation was 30% which is on the low side.  The fact that the transferrin saturation was on the low side was an indicator of a mutation on the FPN gene i.e. SLC40A1.

What are your ferritin and transferrin saturation results?

The treatment is the same in that you have regular phlebotomies but there is a difference in the frequency of the phlebotomies if you have ferroportin disease.  This is because ferroportin disease does not respond well to phlebotomy and the interval has to be longer than classic HH.  I was bled every fortnight and had to move to three weekly for a while because my hb dropped and I was becoming anaemic.  Also, the amount of blood taken is less, I have 350ml removed and not 450ml.

Marie

7

It's funny because this was the case I made to my doctor that frequency and volume each phlebotomy would be different and he disagreed suggesting that we are watching hemoglobin levels regardless of whether my ferritin is high from HFE, SLC or any other gene and he would tweak the frequency and volume as necessary regardless. In my opinion, this is horrible and just a way to save the insurance industry from funding these gene tests. I also made the case that I want to be able to confirm that my organs are salvaged, whereever the iron is. I've tested my liver and heart and no excess iron was found. I believe most of it is sitting in my spleen and spine but I'm not going to continue to test those on a "witch hunt" for the iron. If SLC was positive, I could narrow the field to those organs and focus on them each year to confirm no cancer, etc. this is my pitch for why this is medically necessary. He disagreed. I am pursuing this now with my gastroenterologist to see if he has a different opinion than my hemotologist.

8

Also My ferritin was 919 and 38% TS

9

Usually, the first organ to load iron is the liver, then the heart, pancreas and so on.  The fact that you have not loaded in your liver or your heart is good news.  According to the order of iron accumulation in the organs, your spleen and spine should be OK.

Ferroportin disease has two forms, a mild one and one that resembles the classic HH form.  I have the mild form which means the organs do not get as damaged as the more severe form.  To give you an example, I had loaded iron in my liver to the point where damage to the organ can happen, my ferriscan showed a reading of 14 when the normal range is 2.  I thought my liver would be severely damaged but ultrasound showed a slight fibrosis. 

Check out ferrorportin on the web, as this disorder loads iron in a different way, in the macrophages. 

Marie

 

10

Thanks Marie. Macrophages are primarily part of white blood cells which are stored in both spleen and bone marrow in your spine ( and to a lesser extent Kupffer cells on your liver). The order of the organ loading you are referencing is with Type 1 HFE hemochromatosis, not ferroportin. My hemotologist confirmed spleen and bone marrow would be most at risk if type 4 is confirmed.

11

That is interesting.

It was when I was having an MRI scan for something unrelated to haemochromatosis that infiltration of iron was found in my bones.  That started my journey to ferroportin disease. 

What happens to the bones and spleen when overloaded with iron?  I do have some painful joints and put that down to the disorder.  It is interesting that my consultant does not seem to be too concerned about the bones and spleen.

 

12

This is a good question and not one that I see answered in the literature. I did think the best confirmation of this was Dr Pietrangelo's publishing at:

onlinelibrary.wiley.com/doi/10.1002/cld.340/pdf

I will do some more research related to iron loading impact in spleen and bone marrow and its impact on those longer term

13

I share your frustration!  I live in Canada, where gene testing for ferroportin disease is not available at all.  There is a provision for arranging out-of-country testing in the province where I live, but my hematologist and a hematologist he consulted said that genetic testing was not indicated in my case.  (My situation is consistent with ferroportin loss-of-function disease:  my highest ferritin was 1438 ug/L with normal transferrin saturation, deironing was carried out by removing 7.45 L of blood over about a year and a half, and I developed low hemoglobin during phlebotomy so that I had to increase the time between phlebotomies to over a month.)  I had asked for genetic testing because

a) if I know the reason I overload on iron, I may be able to learn more that will help me understand what tissue damage may already have been caused (I am postulating some sort of damage because although I stopped getting worse once I started phlebotomy, I didn't get better) and possibilities for correcting or at least treating the results of the damage, what my maintenance ferritin target should be to prevent further tissue damage, and what the implications of my disorder might be on handling of minerals other than iron, and

b) I will be able to advise my family members, including my children, on the implications of my diagnosis for them. 

Unfortunately, I guess these reasons weren't considered adequate, so I am now trying to find some other way to get tested.

If you are an American citizen, you might be eligible to participate in a iron metabolism disorders study in the US?  If that turned out to be possible, you wouldn't have to pay for testing and you would be helping increase knowledge about iron disorders. 

I found one study on the Clinical Trials website that says it's currently recruiting ( https://www.clinicaltrials.gov/ct2/show/NCT00102245?recr=Open&no_unk=Y&cond=hematologic&spons=NIDDK&rank=2) : “Clinical and Laboratory Investigation of Humans With Informative Iron or Erythroid Phenotypes . . . Patients of all ages with red cell abnormalities in the following categories may be eligible for this study:  Diseases with deficiency, overload or maldistribution of iron . . . “

You might also want to check if the Finberg Lab at Yale (http://medicine.yale.edu/lab/finberg/index.aspx ) has a iron metabolism disorders genotyping study underway for which you would qualify.

The centerwatch site (https://www.centerwatch.com/clinical-trials/listings/condition/403/iron-overload-hemachromatosis ) isn’t showing any trials on iron overload right now, but you can sign up to be alerted if a new study on iron overload is posted.

I hope some of this might be helpful for you -

14

Marie and Abittight,

Since both of you tested positive, does this mean one of your parents also had this and likely had similar ferritin issues? I ask this because it's autosomal dominant and highly penetratable. Before I get tested, I am thinking I should have my parents test their ferritin levels. My father's is not high and my mother's results are pending.

15

Hi..For what this is worth, Dr, Marshall on radio says one can remove the iron from the liver by eating 3 to 4 dried apricots/day..Soak in water 20 minutes before consuming. He is a reputable man, and I do this.So far, blood tests show ok for liver.

16

Hi,

I agree as Ferroportin Disease is autosomal dominant, one of your parents must carry the faulty gene, I was tested for C282Y and H63D which are the classic faulty genes for Haemocromatosis and was negative for both - I was very lucky as high ferritin was diagnosed when my daughter became pregnant >3000 at the age of 23, they requested that both me and her mother were tested, her mother ferritin is normal, they are almost certain that she has Ferroportin Disease too, her conformation should come through shortly, they have now requested my father to be tested, sadly my mother is no longer alive, which is where I believe the faulty gene has come from, maybe wrong time will tell….

Richard 

17

It does mean that one of my parents had this gene, which one, I don't know.  They both died before I was diagnosed.  My mother died quite young at the age of 47 and I lost my dad nearly 8 years ago.  Mum had a heart attack and dad lung cancer.  He was 72. 

My sister has also inherited this gene and my brother has not been tested for it.  His ferritin levels are nearly 300 so the medical profession think he is OK.

We think that we have inherited from our mother's paternal line.  Her father died in his early 60's and her uncle in his mid 50's.  Her uncle had a heart attack.  A fit man, cycled everywhere, did not drink or smoke.  HIs daughter, my mum's cousin is being tested for the gene, but I don't know the result yet.  I have many cousins and none are showing signs of the symptoms, or at least that is what the say.  They have decided not to get tested. 

It is frustrating not to know for sure which side of the family it is.  I can only wait and see if any of my cousins get diagnosed with it. 

 

18

Hi Marie,

Sorry to hear about your Mom. Thats a shame she died so young and I'm sure thats why you suspect you inherited the gene from her side.  My father had two uncles die early (late 30's and early 40's) and we suspect the same.

My father has a ferritin around 200 and my mom 57. My father is a carrier for H63D and my Mom a carrier for C282Y. I have one of each and confirmed for Type 1 hemochromatosis.

My mom's ferritin of 57 just came back this morning. I also got some bloodwork today that I didnt realize was taken right before I started phlebotomizing that said my ferritin was 812 and saturation % was 50% (I had another one prior to this that said ferritin was 919 and saturation was 38%).

All in all, I am getting more comfortable with a Type 1 hemochromatosis diagnosis this week. With my revised saturation %, I think its more typical for Type 1 rather than ferroportn disease. And my mother and father dont have high ferritin so its unlikey they have the SLC mutation because 85% of people with it generally load iron. so I am not going to go forward with the SLC gene test after all. 

19

From what you say, it sounds like it is more typical for Type 1.

I hope your phlebotomies go well and that you soon get down to your target.

Best wishes

Marie