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.