Description:

There are several causes of macrocytic anemia, including both megaloblastic and nonmegaloblastic processes. The distinction between megaloblastic and nonmegaloblastic macrocytic anemia hinges on the presence or absence of megaloblastic changes affecting erythroid, granulocytic and megakaryocytic lineage maturation in the bone marrow. These characteristic changes in megaloblastic anemia are the result of a defect in DNA synthesis arising from a deficiency or imbalance in the nucleotides required for DNA replication. This chapter is restricted to consideration of megaloblastic anemias, the hallmark of which is a dyssynchrony between nuclear and cytoplasmic maturation. Discussions are focused on the incidence, etiologies, and clinical and laboratory findings, followed by brief case examples of this unique and historic disease.Many factors have been associated with venous thromboembolism. Among them, vitamin B12 deficiency can produce elevated homocysteine levels, which is a risk factor for venous embolism, since the latter interferes with the activation of Va coagulation factor by activation of C protein. We present a case of a patient with metabolic syndrome with apparently unprovoked pulmonary embolism. After careful evaluation, megaloblastic anemia was detected. Even though the patient had biochemistry findings of hemolysis and blood smear did not showed fragmented erythrocytes, which is consistent with pseudo-microangiopathic haemolytic anemia. Cyanocobalamin (Vitamin B12, VB12) and Folic acid (Vitamin B9, VB9) deficiency leads to anemia in women. We have recently shown low VB12 and VB9 levels in the serum of megaloblastic anemia (MBA) patients. Further, our study demonstrated elevated homocysteine and p53, respectively, in the serum and bone marrow aspirates of MBA patients but not in non-MBA subjects. However, it is unknown whether any gender specific variation in VB12 and VB9 level exists in MBA and non-MBA patients? In addition, it is unclear whether low VB12 and VB9 has a role in the regulation of p53 expression in MBA patients? And whether elevated p53 is functionally active? If so, does bone marrow aspirates of MBA patients show elevated apoptosis. Hence, we have analysed VB12 and VB9 levels in MBA patients and compared with non-MBA subjects. Next, methylation status of p53 promoter was determined and correlated with p53 expression.

Furthermore, the level of apoptosis in bone marrow aspirate paraffin blocks was estimated using TUNEL staining. In conclusion, low VB12 and VB9 in male and female patients directly correlate with p53 promoter unmethylation status, but, inversely correlate with p53 protein expression and its activity, only in MBA cases but not in non-MBA controls.  Folic acid and cobalamin are B-group vitamins that play an essential role in many cellular processes. Deficiency in one or both of these vitamins causes megaloblastic anaemia, a disease characterized by the presence of megaloblasts. Megaloblasts occur when inhibition of DNA synthesis causes asynchronous maturation between the nucleus and the cytoplasm. Clinical manifestations are similar to those of other types of anaemia, with the exception of cobalamin deficiency megaloblastic anaemia, which presents distinctive neurological symptoms. An understanding of the metabolism of these vitamins will enable clinicians to make the best use and interpretation of laboratory studies and monitor therapeutic strategies, which consist mainly of administering supplements to restore body reserves.  Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive syndrome characterized by early-onset anemia, diabetes, and hearing loss caused by mutations in the SLC19A2 gene. We studied the genetic cause and clinical features of this condition in patients from the Persian population. A clinical and molecular investigation was performed in four patients from three families and their healthy family members. All had the typical diagnostic criteria. The onset of hearing loss in three patients was at birth and one patient also had a stroke and seizure disorder. Thiamine treatment effectively corrected the anemia in all of our patients but did not prevent hearing loss. Diabetes was improved in one patient who presented at the age of 8 months with anemia and diabetes after 2 months of starting thiamine. The coding regions of SLC19A2 were sequenced in all patients. The identified mutation was tested in all members of the families. Molecular analyses identified a homozygous nonsense mutation c.697C > T (p.Gln233*) as the cause of the disease in all families. This mutation was previously reported in a Turkish patient with TRMA and is likely to be a founder mutation in the Persian population.

With Regards

Willson
Journal Coordinator
Global Journal of Research and Review