Diagnosis

Introduction.

In a patient with a serum B12 level of 70 pmol/L combined with a macrocytic blood count and anemia, a folate level of 3 nmol, and severe (neuro)psychiatric symptoms, diagnosing B12 and folate deficiency need not be difficult. We say “need” because eight people in 2016 in the Netherlands died unnecessarily from B12/folate deficiency (CBS, Feb. 2016).

The diagnosis is also not difficult to make in a patient with a serum B12 level of 100 pmol/L and no anemia, who walks poorly because of muscle pain in the thighs, has tingling in the feet, has joint tenderness, is mildly depressed, has blurred vision, and has a previously diagnosed hypothyroidism: B12 deficiency.

Is diagnosing B12 deficiency complicated?

According to the NHG, no “gold standard test” exists for diagnosing functional B12 deficiency.

What does that mean?

• B12 level below 148 pmol/L with symptoms: B12 deficiency (NHG 2024, WHO 2013, NICE 2024).
• B12 level: between 148 and 250 pmol/L, with symptoms, check MMA and homocysteine. Elevated levels of MMA and Homocysteine? B12 deficiency (NHG 2024, WHO 2013, NICE 2024). Normal MMA/Hcy after treatment: no validity.
• Treatment: B12 def and mild symptoms: tablets (monitor!!). Apparent/severe neurological symptoms? Then, injections are indicated (NHG 2024).

This is what is meant, so the diagnosis can be made quite clearly with laboratory tests and is not as fuzzy as is often thought.

So, what’s up then?

• Sometimes, the difficulty occurs when patients have already had treatment or supplementation. The NHG also states that the B12 values are unreliable because they always will rise.’
• What also makes it difficult, which is not generally known to the health care provider and is warned about by the NHG, is that there need not be hematologic abnormalities in symptomatic B12 deficiency. Anemia with elevated MCV – the classic diagnostic tool – is absent in many cases. The literature and clinical practice show that neurological symptoms can sometimes be more severe without the patient having anemia.
• Normal levels of B12 with underlying functional B12 deficiency can also occur in liver or kidney diseases.
• High Homocysteine (and MMA) occur in kidney diseases, low vitamin B6 and Folic acid, so rules this out, too! We do!

Please also read our Pitfalls page!

>>https://b12-institute.nl/en/diagnosis-and-treatment-pitfalls/ 

World Health Organisation 

The standard generally applied by the WHO (World Health Organisation) is a minimum serum total B12 level of 150 pmol/L; therefore, a serum b12 < 150 pmol/L means a B12 deficiency. Some people with a low serum B12l/L) level (<150 pmo don’t show any symptoms at all; although they are considered deficient by the WHO, they are not being treated by our specialists at the B12 Institute. We do give them information as a preventative measure.

Researchers have started to raise concerns about the long-term consequences of patients with a low serum B12 level without symptoms. In Israel, everybody over 65 is screened preventatively for B12 deficiency. If they show symptoms and serum B12 levels below 150 pmol/L and between 0 and 200 pmol/L, they are treated with injections immediately.

Literature studies prove that values between 150 and 300 pmol/L may undoubtedly point to a functional deficiency, irrespective of a person’s age. If a person has such values, combined with symptoms, MMA and homocysteine levels can be included since these levels may be raised due to a functional B12 deficiency. Recent research results, however, show that patients with B12-deficiency-related symptoms and serum levels between 150 and 200 pmol/L benefit from supplementation despite the (normal) MMA values. This is also seen in clinical practice. 

The Dutch College of General Practitioners (NHG) points out that testing for B12 values after or during B12 supplementation makes no sense since the biochemistry does not correlate with the symptoms during that process.

Testing for MMA and homocysteine after supplementation is also not very useful for the same reason as testing B12 levels. 

BUT: Testing MMA and Homocysteine during treatment can sometimes be helpful if these values are very high during diagnosing B12 def. in our healthcare facility. Another metabolic disease may present, so we refer you to other specialists. If that is the case, we continually monitor the MMA or homocysteine. If it remains high and we cannot get these values down properly, and you continue to have symptoms, then we will refer you to the metabolic disease department of a UMC to rule things out.

We are working towards a protocol for determining a functional deficiency and mapping out the symptoms and the severe consequences of B12 and folate deficiency. Therefore, it is necessary to consider the patient’s symptoms and the medical history of themselves and their relatives, even when they arrive with levels between 150 and 220 pmol/L (marginal or subnormal) or between 220 and 300 pmol/L (normal). Testing MMA and homocysteine (PRE-suppletion!) is then a must.

Diseases with similar symptoms (such as e.g. thyroid diseases, and Lyme disease) must be excluded before patients approach us.

Hematology (blood count)

Earlier tests are also very relevant for a patient’s medical history, but we need the most recent lab results (pre-treatment!!). If the results are not up-to-date or incomplete, we can have you tested in the STAR laboratory on the other side of the street at the B12 Institute. We monitor specific values in cooperation with STAR or Erasmus MC laboratory on special occasions during our health care process. Costs will be on our account since the test is part of our medical specialist care and falls within our DOT/ DBC (transparency of diagnosis -Treatment – combination policy).

Symptomatology

All symptoms observed in a patient will be recorded, filed, and submitted to your file.

Personal medical history

During your treatment, we will take your personal medical history into account.  

Medical history of relatives

We will also consider any relevant family medical history of genetic disorders.

Treatment:

In our health care facility, you always get CUSTOMIZED patient treatment! Because no patient is the same!