What is May-Hegglin Anomaly?
The May-Hegglin anomaly (MHA) is a rare disease that you can inherit from your parents. It is caused by a mutation, or change, in a gene called MYH9. This condition affects your neutrophils – a type of white blood cell – which have unusual inclusions or particles in them. You might also have larger than normal platelets (blood cells that help to form clots) and an unpredictable number of these platelets, which is referred to as variable thrombocytopenia.
May-Hegglin anomaly is part of a group of conditions caused by a defect in the same gene, known as the myosin heavy chain (MHC) group. Other diseases in this group include Fechtner syndrome, Sebastian syndrome, and Epstein syndrome. These conditions all feature large platelets, unique inclusions in leukocytes (another type of white blood cell) resembling Dohle-like bodies, and a mix of other symptoms. Those symptoms could be sensorineural hearing loss where the damage lies in your inner ear, early development of cataracts which can cloud your vision, and renal failure which means your kidneys stop working properly.
What Causes May-Hegglin Anomaly?
The MYH9 gene, which is altered in certain conditions, is found on a specific location on chromosome 22. This gene is responsible for making a protein called NMMHC-IIA, which can be found in various tissues in the body, including platelets – the blood cells involved in clotting.
Researchers have discovered at least 33 different changes or “mutations” in this MYH9 gene. These mutations result in abnormal production of the NMMHC-IIA protein. This abnormality leads to a condition known as macrothrombocytopenia – a disorder where the size of platelets in the blood is larger than normal and the number of platelets is lesser than usual. This condition happens because the mutation in the gene interferes with the normal development and splitting of megakaryocytes, which are the cells that give rise to platelets.
Additionally, these mutations can cause some cells like eosinophils, neutrophils, and monocytes (types of white blood cells) to produce unusual crescent-shaped bodies within the cell, known as Dohle-like inclusion bodies. These bodies are made of the altered NMMHC-IIA protein.
Despite these abnormalities, the functions of neutrophils and platelets – cells critical for immune responses and blood clotting – are usually considered normal.
Risk Factors and Frequency for May-Hegglin Anomaly
May Hegglin anomaly is a seldom seen condition, with only a handful of cases reported. Initially discovered by German doctor May in 1909, and later by Swiss doctor Hegglin in 1945, the overall number of people affected globally is still uncertain. However, less than a hundred cases have been documented in medical records till now.
Signs and Symptoms of May-Hegglin Anomaly
In cases of MHA, a type of blood disorder, physical symptoms may not always be evident. Around half of affected individuals do not show any symptoms. However, the other half may have lower platelet counts (less than 50 K/uL) and abnormal bleeding. The signs of MHA can range and depend on the severity of the condition, such as:
- Nosebleeds
- Easy bruising
- Bleeding of the gums
- Heavy menstrual bleeding
- Excessive bleeding after surgery
Most times the bleeding is mild and does not require specific treatment. However, in some instances, especially after surgery, the bleeding can be severe and require blood transfusions. It’s important to note that there have been no reported cases of bleeding leading to fatal outcomes.
Testing for May-Hegglin Anomaly
If your doctor suspects that you have May-Hegglin anomaly (MHA), a rare blood condition, they will likely order a complete blood count (CBC) and check the form and shape of your blood cells under a microscope. Additionally, they might ask about any family history of abnormal bleeding, which can be a clue to diagnosing MHA.
Looking at your blood under a microscope (a process called a peripheral smear) could reveal some irregularities in your white blood cells and platelets. These irregular cells might contain unusual structures (cytoplasmic inclusions) that can resemble Dohle bodies, typically found in neutrophils, monocytes, eosinophils, and basophils. These inclusions aren’t found in platelets, which might look much bigger than normal. Sometimes the presence of larger platelets can lead to an underestimation of the platelet count by automated analyzers. In such cases, the platelet count can be better assessed based on evaluating the peripheral blood smear.
Another test, an electron microscopy, reveals that the platelets have an unusual shape due to the presence of abnormally organized microtubules (tiny structures within the cell).
Your doctor may also examine your bone marrow, the spongy tissue inside your bones where blood cells are made. In people with MHA, the number and appearance of megakaryocytes (the cells that produce platelets) are normal. However, it’s believed that these cells don’t divide properly into platelets, causing a decrease in platelet count.
Despite these irregularities, most people with MHA will exhibit normal patterns of platelet clumping (aggregation) and ATP secretion, the process by which energy is transferred in cells.
Other signs of MHA might include prolonged bleeding times, related to the reduced number of platelets, and the presence of inclusion bodies in leukocytes (a type of white blood cell), which help to rule out immune-mediated low platelet count. Genetic testing for the MYH9 gene mutation can confirm the diagnosis of MHA in uncertain cases.
Your doctor might also consider other conditions that have similar symptoms to MHA. If they suspect conditions with features such as hearing loss, cataracts, and kidney disease, they might perform an audiogram, test your kidney function, and conduct an eye examination. Genetic tests could potentially assess the risk of these conditions, although this is still debated in the medical community.
Treatment Options for May-Hegglin Anomaly
Most individuals with certain blood disorders often don’t experience significant bleeding complications. In some cases, their condition is only discovered during health checks for other unrelated issues. For a majority of these patients, specific treatment isn’t required.
However rare, instances of severe bleeding can occur. In such situations, a blood product infusion known as a platelet transfusion may be necessary. This is similar to a blood transfusion but only involves platelets, which are blood cells crucial to forming clots and stop bleeding. If surgery is needed, it might safer to do a preventive or prophylactic platelet transfusion. In these cases, it’s important to involve a blood disease specialist, known as a hematologist, in the decision-making process.
Desmopressin, which is a medication that can help to prevent bleeding complications, is an option for patients who need a specific type of surgery called a craniotomy (surgery on the brain). However, this is done carefully to avoid the need for a platelet transfusion.
It’s worth noting that treatments such as administering corticosteroids (anti-inflammatory medication), immunosuppressive agents (medication that reduces the body’s immune response), or carrying out a splenectomy (surgical removal of the spleen) are not appropriate for this condition.
What else can May-Hegglin Anomaly be?
There are numerous conditions and medical situations that might require special examination. These include:
- Alport Syndrome: A genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.
- Bernard-Souliere syndrome: A rare disorder that affects platelet function, leading to a bleeding tendency.
- Dohle bodies: These are small blue-gray inclusions sometimes found in white blood cells, usually from an emergency response to an infection.
- Greaves syndrome: A rare health condition often identified with significant skeletal abnormalities and intellectual disability.
- Megaloblastic anemia: A blood disorder in which the bone marrow produces unusually large, immature red blood cells.
- Septicemia: A severe infection that spreads through the bloodstream, also known as sepsis.
- Pregnancy: The period from conception to birth.
- Thrombopoiesis: The process of producing platelets, which are important for blood coagulation.
- Thrombopoietic deficiencies: Conditions characterized by a low platelet count, which can result in problems with blood coagulation and a higher risk of bleeding.
