Nowadays, we know that Diamine Oxidase deficiency (DAO deficiency) may be primary or secondary, which is the same as saying genetic or acquired. Therefore, DAO deficiency can be hereditary and in fact it is its main cause.
It is important to remember that what we inherit is the enzymatic deficiency but not the symptomatology. In the same family we can find people with DAO deficiency, but with different associated symptoms. For example: a mother with migraine and non-allergic rhinitis, a son with hives and digestive disorders and an uncle with chronic fatigue and digestive disorders.
AOC1 is the gene that codes for the synthesis of the DAO enzyme. When there is a genetic alteration in AOC1, the DAO enzyme produced has an abnormal structure and, consequently, less effective in its main function: the degradation of histamine from the diet.
What test should I request for?
To know if the DAO deficiency has a genetic origin, a molecular genetic study of Diamino Oxidase deficit must be performed. In this study 4 variants of the AOC1 gene are studied, which, in scientific literature, have been associated with reduced levels of DAO activity with a lower capacity for histamine degradation:
- AOC1 c.47C>T (p.Thr16Met)
- AOC1 c.995C>T (p.Ser332Phe)
- AOC1 c.1990C>G (p.His664Asp)
- AOC1 c.691G>T
For all variants, a CC result indicates a normal production of the DAO enzyme, while a CT, CG, TT or GG result indicates an abnormal production of the enzyme and therefore a higher risk of DAO deficiency. In addition, the p.T16Met variant has been associated with an increased risk of hypersensitivity to NSAIDs (Non-Steroidal Anti-Inflammatory Drugs, such as Acetylsalicylic Acid or Ibuprofen. In turn, they inhibit the function of DAO activity).
Below, we show the main differences between the genetic test and the enzymatic activity test:
Genetic test (+info) |
Activity test |
| It reports the existence or not of a genetic alteration for the formation of the DAO enzyme | It measures the enzymatic activity of DAO at the time of analysis |
| It is evaluated in blood or oral mucosa (non-invasive) | It can only be evaluated in blood (invasive) |
| It is evaluated in DNA | It is evaluated in blood plasma |
| It is measured in variants of G, T and / or C alleles | It is measured in HDU/ml o U/ml units |
| Normality: Negative (CC for all variants) | Normality: >80 HDU/ml or >12,54 U/ml |
| The result does not vary. It is done once in a lifetime | The result varies from one take to another |
| The result is not influenced by external factors | The result may be influenced by several factors: taking drugs, drinking alcohol, intestinal inflammation, surgical interventions, menstrual period… |
| It is not covered by Social Security and it costs around 120€ (a few years ago it cost more than 300€) | Some autonomous communities or private health insurances cover it and costs around 70€ |
| It must be prescribed by a healthcare professional | In some laboratories the patient can request the test without prescription |
Until the beginning of 2019 we only had the option to recommend the DAO activity test, because the genetic test was very expensive. But now, thanks to a more modern technology, we consider very interesting to ask the genetic test for all our patients, specially if there exist family history. With a sample of oral mucosa we can know if there is any genetic polymorphism and therefore, intuit how the patient’s DAO activity will evolve and which treatment will be the most appropriate.
So, if the genetic test is positive, will I never be cured?
To suffer DAO deficiency with a genetic origin means that, by genetics, an enzyme with abnormal structure will always be produced and not at all effective. Even so, the levels of enzymatic activity not only depend on genetics, but also are influenced by other secondary factors (intestinal inflammatory diseases, taking of certain DAO enzyme blocking drugs, consumption of alcoholic beverages, surgical interventions, menstrual period, etc.). Therefore, the levels of enzyme activity can be improved to a greater or lesser extent with a healthy lifestyle and taking into account these factors together with a specialized professional. But if the genetic factor exists, it will be essential to follow a low histamine diet more or less strict throughout life to control the symptoms.
In AD Dietistas we managed to see a great improvement in the majority of the patients we visit, either because they have a genetic and/or acquired DAO deficiency. If you want us to advise you in a personalized way, either in our Barcelona centre or by videoconference from anywhere in the world, contact us and we will help you.
Looks like myself and my identical twin have Dao deficiency. All the classic stuff listed above applies to us. Bananas are horribly painful to digest. Beer and wine cause congestion followed by a bad headache and super stuffy nose. I am now a non alcohol drinker. Have a latex allergy too. Also allergic to sulphur and animal dander. Asthma too. I can eat avocado in small amounts and Tom soup is one of my fav. But by the time I get to bed I am a mucous mess! My poor husband! So any further insights would b appreciated. Is pinyon or hemlock or kapok tree allergies related in any way? Thank you
Hi Leanore,
Sorry for my delayed answer.
It is common to react to all these rich histamine foods if you have, in addition, allergies. So in my opinion you could do some clinical tests (saliva, blood and urine) and depending on the results you should follow a low histamine diet. It looks like you may have DAO deficiency.
I don’t know if these trees are related between them. But in any case, if you have allergy to them, they may increase your symptoms when you eat rich histamine food.
If you need any other information or if you need to schedule an online appointment please, do not hesitate to contact us through our patient care email info@adrianaduelo.com.
Kind regards!
Hi Leanore,
Reading your symptoms could be a case of excess histamine due to a deficit of DAO.
This fact causes that you can´t eliminate correctly the histamine that you ingests through your diet. That’s why our recommendation is to go to a nutrition professional to give you a personalized low-histamine and healthy diet. It is very easy, in this type of diet, to make too many restrictions and to make nutritional deficiencies.
In the case of not finding professionals, you can request a visit with our team. We visit online all over the world.
Allergies and DAO deficiency do not necessarily go hand in hand. Each case must be treated individually.
King Regards!
I’m so glad to find your site. I’m hoping you can clarify something for me. I was reading another website and it says: “DAO deficiency can be caused by genetic factors (primary deficiency) when certain sequence variants (polymorphisms) in the DAO gene lead to a significantly reduced DAO enzyme activity. Individuals with a DAO gene mutation may have a tendency towards high histamine. Having a polymorphism doesn’t mean you will have expression of the SNP and therefore histamine intolerance, but you are pre-disposed, particularly if your environment (food, stress, toxin exposure, gut function) are affecting the expression of the gene.”
Is that correct that having a polymorphism doesn’t mean you’ll necessarily have expression of the SNP? I thought that if you have a SNP in the DAO gene (or genes), you’ll definitely produce less DAO than if you don’t have a SNP—but having a SNP does not necessarily mean you’ll develop histamine intolerance. It sounds like this person is saying that if you have a SNP in a DAO gene, the SNP might not express and you therefore might not have reduced DAO production. Can you please clarify? Thank you!
Hi Chloe,
Basically, having a positive genetic test result tells us that the patient has a genetic predisposition to suffer DAO deficiency. Obviously, without symptoms there is no problem, but if we add symptoms to a positive result we have the diagnosis of deficiency. The enzyme activity may vary from one moment to another even within the same day…. I hope I have answered your question.
Best regards!
Genetic test revealed DAO His645Asp C>G CG and HNMT 939 A>G AA. I don’t see any mention of A0C1 on my report findings. Do the DAO &/or HNMT findings tell us anything about genetic susceptibility to histamine intolerance etc or did I need to get the AOC1 gene itself tested?
Experiencing severe menstrual migraines in perimenopause and considering low histamine diet or other gameplay around histamine reduction to see if that helps reduce symptoms. Hoped this 3×4 genetics test would offer insight but confused by your informative post above. Thanks!
DAO gene is another name for AOC1 gene. https://www.ncbi.nlm.nih.gov/gene/26