Chances are that you have probably heard of anaemia. But what exactly is it? And what is sideroblastic anaemia (SA)? In this article, we will discuss this disorder in detail and try to pre-empt and answer any questions that might arise in your mind. 

Briefly, SA is a rare blood disorder,  in which your body is unable to utilise iron to produce red blood cells. In order to understand this better, we will first explain red blood cells and their function in the human body. 

Understanding sideroblastic anaemia

Red blood cells in our bodies are produced by our bone marrow and utilise iron to form a protein called haemoglobin. Haemoglobin is found in red blood cells and it carries oxygen all around the body. When there is a lack of red blood cells or haemoglobin in our bodies, the condition is called anaemia. 

In SA, the issue lies with the ability of the body to utilise the iron to produce an adequate amount of haemoglobin. Without enough haemoglobin, there will be a consequent decrease in the oxygen-carrying ability of the red blood cells, and the body won't receive enough oxygen. 

Another problem, which occurs in SA, is that the unused iron builds up in the bone marrow causing the production of immature red blood cells that contain a high amount of iron. This excess iron forms rings around the centre of the cells, and these are seen as “ringed sideroblasts”.¹ 

Types of sideroblastic anaemia

Hereditary 

This form of SA is quite rare. The most common form of its inheritance is X-linked, which means that you can inherit it from either parent. In this form, there is a mutation (change in the structure of a gene) in the gene that is involved in the production of haemoglobin; hence, haemoglobin is not produced properly and cannot carry out its function of oxygen transportation. As a complication, your body starts to absorb more iron from the gut and this results in an iron overload in the body. This condition can be dangerous and it causes significant damage to the body's organs,  in particular the liver. The hereditary form of SA is usually diagnosed during early adulthood. 

This X-linked form of SA can show the typical symptoms of SA (listed below,) but there may also be additional symptoms of excess iron in the body. These symptoms include an enlarged liver and spleen, which can cause dull abdominal pain. There can also be a bronze tint to the skin and the development of diabetes mellitus. 

There is also an autosomal recessive form, which is the second most common form and mostly affects young children. Unfortunately, this form can be quite serious and needs urgent medical intervention. 

The  least common hereditary form is the maternal type. It involves a mutation in the gene that is responsible for mitochondrial function. 

Acquired 

The acquired form can be further divided into primary and secondary forms. The primary form of acquired SA is associated with myelodysplastic syndrome. The secondary type usually develops after exposure to certain substances, or a deficiency in a necessary molecule or mineral. These factors include:

• Alcohol. Overconsumption is the most common cause of acquired SA
• Vitamin B deficiency. This is because vitamin B aids the formation of haemoglobin, and a lack of this vitamin can impair its function 
• Heavy metal poisoning, such as with arsenic and lead
• Reduced copper. This is because copper helps to produce a specific enzyme which can protect the body against elevated iron levels
• A high level of zinc. Zinc can affect copper absorption as well as impairing the body's use of iron 
• Chemotherapy 
• Medications such as antibiotics, and medicines that help to eliminate copper from the body 

Signs and symptoms

SA involves the impairment of the body's function to provide the body and its organs with a vital supply of oxygen. Symptoms arise when the body's oxygen needs are not being sufficiently met. These symptoms can be similar in all forms of anaemia and are:

• Tiredness, weakness and fatigue
• Irritability 
• Frequent headaches
• Pale skin
• Tachycardia (heart rate faster than normal) and palpitations (noticeable fluttering or pounding heartbeat)
• Chest pain
• Dyspnea (shortness of breath)

Diagnosis and evaluation

The symptoms of SA are very similar to the symptoms of anaemia in general so its diagnosis can be a little tricky. 

First of all acquired SA needs to be ruled out; your doctor might take a detailed history to recognise any triggering factors. If acquired SA is ruled out, more tests might be needed to determine which type of hereditary SA is present. 

Several blood tests must be conducted such as a CBC (complete blood count) and peripheral blood smear, in order to determine the number, size and width of your red blood cells. The levels of iron will also be required to check if it is raised. 

In some cases, more invasive tests might be ordered by your doctor such as a bone marrow aspiration and biopsy  to check for the presence of abnormal cells. This can indicate acquired primary SA due to myelodysplastic syndrome. Genetic testing may also be deemed necessary in some cases in order to diagnose hereditary forms of SA which occur due to specific mutations. 

Management of SA

The treatment of SA largely depends on what is causing it and which type of SA is present. If the hereditary form is present, your doctor may treat the condition with oral pyridoxine (vitamin B6). A dose of 50–100 mg/day has been proven to be sufficient to correct the anaemia present in this condition. However, if the symptoms persist or if the anaemia is severe or unresponsive, then a blood transfusion may be needed. Along with a blood transfusion, the iron levels in the body will need to be controlled by administering deferoxamine (an iron chelator) which helps rid the body of excess iron . A bone marrow transplant may be considered as a last resort, if the SA is not responding to any treatment. 

If the cause of SA is exposure to certain toxins, heavy metals or drugs, then the exposure to this substance needs to be immediately discontinued and the patient will be treated according to the exposure. The SA will automatically improve after discontinuation of the causative drug or toxin. 

If the SA is secondary to increased zinc levels or reduced copper levels, then the levels of these minerals need to be corrected. 

In the acquired primary form of SA, the underlying myelodysplastic syndrome needs to be treated. 

Prognosis 

The prognosis of SA is largely dependent on the underlying cause. In the secondary acquired cases, the prognosis is good because the condition can easily be treated by correcting the underlying cause or avoiding exposure to particular toxins. 

In hereditary causes, the prognosis is also good but continuous monitoring of the condition is usually required. Iron levels need to be closely controlled and appropriate pyridoxine levels need to be achieved. If the iron levels remain high, iron can accumulate in the liver, eventually causing fibrosis and cirrhosis. Thus, if these levels are not corrected, the prognosis can be poor. 

Prevention 

The hereditary form of SA is passed on from your parents and there is little you can do to avoid inheriting it. If this form of SA is present, the best you can do is to manage it  properly. A very strict medication compliance is required with strong adherence to pyridoxamine supplements and iron chelators such as deforoxamine. In addition, care needs to be taken to avoid iron–rich food, in order to avoid further iron loading. 

Genetic testing should also be available for families who exhibit the inherited form of SA, so that proper management measures can be arranged by the medical team. 

The acquired form of SA can be prevented. Alcohol should not be consumed in excess and any zinc supplements should be taken at an appropriate dosage under medical guidance. Accidental arsenic and lead poisoning should be carefully avoided. Furthermore, a healthy and well-balanced diet should be established to ensure proper intake of all nutrients. 

Summary 

SA is a type of anaemia which exhibits very similar symptoms to other types of anaemia. In this condition, your body is unable to properly utilise iron and thus the oxygen-carrying ability of the body is reduced and this causes the symptoms associated with this condition. 

The symptoms of SA can be very similar to general anaemia, and thus, it can often be mistaken for another type of anaemia. Proper diagnostic tests need to be conducted in order to avoid a misdiagnosis.

There are two main forms, acquired and hereditary; the acquired form develops secondary to a cause and the hereditary form is inherited from a parent. The acquired form of SA is easier to manage, as the factor causing it just needs to be avoided. The hereditary SA needs proper management with pyridoxamine supplements and continuous monitoring of iron levels. A high blood iron level can be very harmful for the body so an iron chelator needs to be added to the management of hereditary SA. Patients and caregivers need to be educated by their doctors on how to properly manage this condition. 

Overall, SA can be properly managed and it does not necessarily carry a bad prognosis. With proper and compliant management,  an affected person can live a normal, relatively healthy life.