Blood is an important factor in our bodies, without which we cannot survive. Just having blood will not suffice. We need good quality healthy blood that consists of four main components – the red blood cells, white blood cells, platelets, and plasma. All these components help in the proper functioning of the entire body, carry oxygen to all parts of the body and protect the body from various types of harm. The white blood cells fight foreign invaders, while the platelets form clots to protect the body from losing too much blood in case of an injury. Red blood cells are what help in carrying oxygen to the entire body.
Have you ever wondered where all these components come from? Yes, we have heard eating certain foods can increase or strengthen the production of certain blood components. But where are they produced? Is there an organ doing this important job? The bone marrow is what produces all these blood cells as well as stem cells. Bone marrow is the spongy organ present inside the bones in your body. Without proper functioning bone marrow, the blood cells produced will not be up to the quality or meet your body’s requirements which can lead to a number of health problems.
Some people do not have a healthy or properly functioning bone marrow. They can have a defect in the bone marrow which can cause problems with the blood cells produced in the marrow. This type of defect can either be inherited or acquired, eventually leading to a lot of diseases and infections that reduce the quality of life. In this review, we will discuss inherited bone marrow failure syndromes.
In This Article
- What is Inherited Bone Marrow Failure Syndrome?
- Types of Inherited Bone Marrow Failure Syndrome in Children
- What Causes Inherited Bone Marrow Failure in Children?
- Signs of Inherited Bone Marrow Failure
- How is Inherited Bone Marrow Failure Diagnosed?
- Treatment Options For Inherited Bone Marrow Failure Syndromes
- When Should I See A Doctor?
- FAQ’s
What is Inherited Bone Marrow Failure Syndrome?
The inherited bone marrow failure syndromes (IBMFS), as the name suggests, are the failure of the bone marrow. This failure can be partial or complete or can be progressive. IBMFS is a group of genetic disorders of the blood and the condition is quite rare.
IBFMS represents a group of genetic conditions where there is an inherited genetic defect that predisposes the individual to develop bone marrow failure. The failure of the bone marrow to produce blood cells is commonly known as aplastic anaemia.
Patients with IBFMS fall under the high-risk category for developing cancer. Some disorders associated with this group will show physical changes in the affected person, which are very typical of these disorders. The results of laboratory tests will also be quite standard and a clear indication of the condition. These syndromes have been well described over the years and are quite easily recognised by health care experts. However, there are not so common disorders in this group, which can be hard to diagnose. Some of these patients will have the symptoms but cannot be easily classified into a category of IBFMS.
Though IBFMS usually presents itself in children, over the years, many adults have been diagnosed with this and many children have successfully reached adulthood despite the condition.
Types of Inherited Bone Marrow Failure Syndrome in Children
Over the years more than thirty types of these disorders have been identified. Some of the most common types of this disorder are:
- Fanconi anemia (FA)
- Dyskeratosis congenita (DC)
- Shwachman Diamond syndrome (SDS)
- Amegakaryocytic thrombocytopenia (Amega)
- Diamond Blackfan anemia (DBA)
- Pearson syndrome
- Severe congenital neutropenia (SCN)
- Thrombocytopenia absent radii (TAR)
Some of the patients who begin with just a single lineage deficiency will eventually end up with full-blown aplastic anemia. Recent studies have found that many of these patients even develop tumors over the course of time. Researchers and doctors are conducting many studies to understand how any of the above-mentioned syndromes develop into full-fledged cancer. Researchers are also collecting details about each of these syndromes to understand which symptoms indicate a clear case of IBFMS. Advances in genetic testing and the wide availability of such techniques help in identifying and classifying these conditions more accurately.
What Causes Inherited Bone Marrow Failure in Children?
Now, let’s try to understand how this rare yet not-so-rare disorder develops in children. Bone marrow failure can be present right from the birth of a child or even develop later in their lives. In most cases, the main cause is an inherited defective gene. The inherited gene defect leads to dysfunction of the bone marrow cells over a period of time, though the defect was inherited at birth. The failure of the bone marrow can be related to just a single cell line or all three blood cell lines or start with a problem in a single cell line and progress to the other cell lines.
A human body has three main types of blood cells
- White Blood Cells: Fight against infections
- Red Blood Cells: Contain haemoglobin and deliver oxygen to the entire body
- Platelets: Help arrest bleeding by forming clots
The bone marrow produces all three cells and is important for the survival of a child. The bone marrow produces these cells and releases them into the bloodstream once they mature. A body must produce a certain quantity of each of these cells to function properly and to maintain sufficient numbers of these cells in the peripheral blood. When the bone marrow does not produce these cells in the required quantities, it manifests as a low peripheral blood count, which may give a clue to the doctors about the underlying bone marrow failure.
Signs of Inherited Bone Marrow Failure
The classic signs of a problem in the bone marrow are weakness and tiredness due to low haemoglobin, recurrent infections and bleeds. When the bone marrow fails to perform its functions, the body is unable to arrest the bleeds due to deficiency of platelets, resulting in easy bruising and extended bleeding when compared to a healthy individual.
Inherited bone marrow failure syndrome affects children of any age most commonly between the ages of 1 and 10 years. Some of the IBMFS conditions affect adolescents between 12 and 20 years of age. It is found in both males and females equally.
So, when does the doctor suspect it could be an IBFMS? How do they decide they need to test for this possibility?
- Many patients or children with IBFMS are born with classic birth defects. They can even have physical abnormalities, which will require further tests.
- Tumors occur at a much earlier stage in such patients when compared to those without the risk of IBMFS.
- Different syndromes have different symptoms. For example, Fanconi Anemia – the most common type of inherited bone marrow failure syndrome in children, has a high frequency of chromosomal breakage which is due to defects in DNA repair mechanisms.
Studies have found a strong connection between FA and DNA repair. Special blood tests help to figure this out.
Similarly, other syndromes have certain classical presentations that help doctors narrow down their suspicions.
Signs of Aplastic Anemia in Children With Inherited Bone Marrow Failure
Children with inherited bone marrow failure can also have aplastic anemia since the bone marrow cannot produce enough blood. In the cases of aplastic anaemia where bone marrow failure has progressed significantly (which is a classical symptom of many IBMFS) in children, you can find the following symptoms:
- Infections (white blood cells are not functioning properly)
- Fatigue (red blood cells are not functioning properly)
- Bruises easily (platelets are not functioning properly)
- Pale skin
- Nose bleeds
Now, aplastic anaemia symptoms can be present in many of these IBMFS. The symptoms of one syndrome can be similar to another. For example – Both FA and DBA will present with symptoms such as pale skin, fatigue, abnormalities in the thumb, and short stature. Though there are certain other symptoms specific to FA or DBA, if the above-mentioned symptoms are present in a child, it can become difficult to narrow down on FA or DBA without further tests. Sometimes symptoms present themselves over time.
[Read : Aplastic Anaemia in Children]
How is Inherited Bone Marrow Failure Diagnosed?
Diagnosing Inherited bone marrow failure Syndrome In Children in time is very important. The earlier the child receives the right treatment, the better it will be to manage the disease and complications stemming from it. Each type of bone marrow failure syndrome has a different protocol when it comes to treatment and care. Most of the patients will require a multidisciplinary team of specialists to help them keep the disease under control.
In the case of IBMFS, once the marrow failure starts, the disease will progress rapidly and will require timely treatment to prevent it from becoming life-threatening. It can also help identify potentially affected family members.
Diagnosing IBFMS can be tricky. The symptoms overlap each other and make it more difficult to make a proper diagnosis without special genetic tests. In some cases, the symptoms presented, and clinical test results will present a standard case. This makes it easier to diagnose.
Steps in Diagnosing Inherited Bone Marrow Failure in Children
The diagnosis of this condition takes place in multiple stages which is explained below.
- The doctor will first identify if it is inherited or acquired bone marrow failure.
- If it is an “acquired” type, they will have to identify if it is indeed bone marrow failure or early signs of cancer or if the bone marrow failure is a manifestation of some other underlying medical condition.
- The doctor will make the final diagnosis only after identifying the pathogen’s mutations in the genes associated with each type of syndrome.
- In some rare situations based on the clinical history, examination findings, lab reports and family history the doctor may make a diagnosis of IBMFS though they were not able to detect any known gene defects on the tests.
- A classic test to confirm bone marrow failure in an IBMFS is a bone marrow biopsy. The biopsy will involve collecting a tissue sample from the bone marrow and testing it. Though the process of collecting this bone marrow sample is mostly a daycare procedure, it can be painful for some children and hence performed under short anaesthesia in children. The reports of the test are available in a few days.
- Telomere shortening conditions will require special tests for a proper diagnosis.
Treatment Options For Inherited Bone Marrow Failure Syndromes
Once there is a suspicion of bone marrow failure whether it is inherited or acquired it progresses rapidly. The doctors cannot wait much longer, as early diagnosis increases the chances of more effective treatments before serious and life-threatening complications occur.
IBMFS may not just affect the blood system, it has implications for other organ systems of the body based on underlying genetic defects. This is why your child will require multi-specialists. These specialists will treat conditions pertaining to their field to prevent further progress of the disease and reduce the impact of the symptoms on other parts of the body.
1. Bone Marrow Transplant
Health care professionals will closely monitor the blood counts to ensure the count does not go too low. When this is not sufficient or not possible, doctors can suggest a bone marrow transplant. This will again depend on the availability of a suitable match.
[Read : Bone Marrow Transplant For Children]
2. Stem Cell Transplant
For some children, if the disease progression is quick and they have a perfect match donor in the form of a sibling or a family member, the doctors might suggest a stem cell transplant at the earliest. This can reduce the impact of the syndrome on the child’s overall health and growth.
In cases where a perfect match is not available, doctors will look for donors outside the family or may consider doing a half-matched transplant with other family members and will also focus on treating the impacts the syndrome has on the body. This will help reduce the complications or at least keep them in check and improve the child’s quality of life.
[Read : Stem Cells Uses, Importance, and Potential Medical Applications]
3. Treating Any Other Existing Infections
If the child’s immunity is very weak and results in multiple infections, the doctors will treat those infections to ensure they don’t affect other parts of the body. Stem cell transplant may cure the bone marrow failure aspect of the inherited bone marrow failure syndromes but not the manifestation in other organ systems.
4. Additional Treatments
Blood transfusions, immunotherapies, chelation therapy, and supportive care are some of the common treatment options to maintain the child’s quality of life until a transplant is possible.
When Should I See A Doctor?
Children fall sick regularly. Parents cannot rush to the doctor for every cough or cold. However, if you notice the following, do take your child to a doctor immediately.
- Your child is more tired than usual, even on days when they don’t physically exert themselves. IBMFS’s classic symptom is fatigue.
- The skin of your child is too pale or is discoloured.
- You notice the spontaneous appearance of bruises in the body or any bleeding symptoms such as bleeding from the nose or gums.
- Your child develops recurrent or prolonged infections more than other children of similar age and regular medications don’t seem to work.
- You notice a growth impact (i.e) your child is not growing tall or has a short stature when compared to other children of the same age.
- There are other physical abnormalities. It can be in the limbs, fingers, cleft palate, etc.
- Hair thinning or greying.
- Foul-smelling diarrhoea that seems to be chronic.
What You Should Know Before Seeing a Doctor
It can be quite tricky to understand if your child might have something more serious than a regular infection. When the child is young, it is advisable to consult a doctor for all infections or concerns. Parents should not take such issues lightly and should never self-medicate a child or ignore conditions.
There is no harm in consulting your doctor a few times for similar infections or symptoms. Only if your doctor realises the frequency is more than usual, can they suspect something and prescribe tests accordingly. Even if you are switching doctors because you are not happy with a doctor’s medications for a certain symptom your child is showing, you need to give a full history of all infections and medications to the new doctor.
If you keep shifting doctors or not telling the new doctor about the past infections or treatments, it makes it difficult for them to even suspect something. Unless suspicion arises, no doctor will ask for a bone marrow biopsy or other complicated tests.
FAQ’s
1. Is Bone Marrow Failure Congenital?
Not all bone marrow failures are congenital. Some can be acquired due to certain treatments or exposure to chemicals or start as an autoimmune process. Sometimes it can even be due to certain drugs or viral infections. Some of the congenital defects associated with inherited bone marrow failure can be present at birth. The bone marrow failure generally manifests at a later time period and is usually not present at birth. Inherited bone marrow failure syndrome is a very rare disease that is passed down genetically from a parent to a child. Generally, the child will show other developmental abnormalities which can affect their growth and quality of life.
2. What Diseases Are Associated With Bone Marrow?
Bone marrow is very crucial for a healthy life. A malfunction of this tissue can lead to many health issues, most of which are chronic and can also be fatal.
Some of the most common diseases associated with bone marrow are
- Leukemia: More commonly known as blood cancer where the bone marrow produces abnormal white blood cells.
- Aplastic Anemia: Failure of the bone marrow to produce red blood cells which can affect the entire body as various body parts will not receive sufficient oxygen.
- Myeloproliferative Disorders: There are many subcategories in this disorder, where the bone marrow does not produce different types of blood cells properly and produces abnormal cells.
- Myelodysplastic Syndrome (MDS): A disorder where the production of normal blood cells is not sufficient and the cells in the marrow look abnormal. This is generally considered as a pre-cancerous state.
- Lymphoma: Cancer in the immune cells that starts in the lymphocytes residing in the lymphatic system and can invade the bone marrow or can start in the bone marrow.
Read Also: Leukaemia in Children – Symptoms, Diagnosis and Treatment by Dr. Stalin Ramprakash
