DISCUSSION
Thalassemia is the most common hemoglobinopathy, almost 5% worldwide have at least one thalassemia defect allele. It is highly prevalent in Southeast Asia, the Asian-Indian subcontinent, and the Mediterranean region [1,4].
It is categorized into major two groups, α thalassemia andβ thalassemia.
α thalassemia is caused by deletions in one or more of the four alpha globin genes. Deletion of two alpha genes causes thalassemia alpha minor (–, αα) or (-α, - α), while loss of three genes results in hemoglobin H disease (–, -α), and deletion of all four genes leads to hemoglobin Barts or hydrops fetalis.
β thalassemia on the other hand, results from mutations rather than deletions in beta globin genes ranging from reduced production of beta chains (β+) and asymptomatic disease as in beta thalassemia trait or minor to absence of beta chains causing severe course of the disease seen in beta thalassemia major (β0) [4]. The absence of beta globin chains results in excess unbound α globin chains that accumulate and precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral hemolysis [1].
TDBT or also known as Cooley’s anemia, refers to the most severe form of the disease where there is minimal to no beta globin chain production and as a result little to absent HbA.
Patients with beta thalassemia major have profound and lifelong transfusion-dependent anemia, which affects their quality of life and performance status, especially among children patients as it largely affects their academic performance as well as their emotional and psychological status [5]. Symptoms typically begin to manifest relatively late after birth (6 to 12 months of age) because major hemoglobin in newborns is fetal hemoglobin (HbF), which consists of gamma chains instead of beta chains. Symptoms include anemia which is severe and profound and if untreated can be as low as 3-4 mg/dl, it’s typically microcytic hypochromic with elevated RBC count. Gallstones formation and jaundice due to chromic hemolysis which also leads to hepatosplenomegaly which can be exacerbated by extramedullary hematopoiesis. Patients who develop cytopenias and shortened survival of transfused RBCs may be evaluated for splenectomy [6]. TDBT as the name implies carries the risks associated with recurrent blood transfusions, especially iron overload that requires monitoring and management by long-term iron chelation therapy to prevent iron-overload complications such as cardiomyopathy and endocrinopathy, which carry high morbidity and mortality rates [7]. However, iron overload is a one complication that paves the way for subsequent serious complications. Osteoporosis is recognized due to different etiologies including chronic anemia, ineffective hematopoiesis and bone marrow expansion, calcium and zinc deficiencies. But the exact mechanism is still not fully understood [8]. Other complications include thyroid disease particularly hypothyroidism, primary rather than secondary [9], as seen in our patient with TSH of 20 mIU/L with no other signs or symptoms suggesting secondary cause, and was started on levothyroxine during admission. Excess iron also leads to diabetes and glucose abnormalities, hypogonadotropic hypogonadism due to chronic liver disease and impaired pituitary axis which also can cause growth hormone deficiency [10,11,12].
Extramedullary hematopoiesis is the production of blood cells outside the bone marrow that typically occurs in liver and spleen and leads to hepatosplenomegaly, although rarely can result in skeletal malformations such as facial deformities and change in body habitus. It also may manifest in the mediastinum and produce symptoms as cough or shortness of breath mimicking thoracic tumors [2]. However, spinal cord compression (SCC) is a rare manifestation of EMH although it may be asymptomatic, EMH-associated SCC can lead to permanent neurological injury, and when that occurs, surgical decompression should be considered with or without radiotherapy, although surgery is not always possible and may carry potential complications [13].
MRI is the diagnostic modality of choice, and biopsy is not always needed to confirm the diagnosis, but when performed it can be CT-guided as was done in our case.[13].
In our patient the main symptom was low back and low abdominal pain, without neurological symptoms. The MRI showed soft tissue mass in the presacral area representing EMH. Patient was started on hydroxyurea and hypertransfusion. Treatment options for EMH at this site is either radiotherapy or surgical excision. Because of the patient’s young age and the risk of infertility, surgical excision was preferred to radiotherapy particularly as the lesion is also well-localized and operable.
The following images show MRI lesions and biopsy results.