Discussion:
Hemolytic anemia is a diverse group of hematologic disorders that can be either congenital or acquired. An extensive workup for identifying an underlying etiology of hemolysis is needed due to the wide range of causes ranging from drugs to autoimmune and infectious to deficiency of B12 or folate. A deficiency of vitamin B12 can lead to megaloblastic anemia. Vitamin B12 is involved in DNA synthesis and red cell maturation [2]. The deficiency of vitamin B12 can lead to hemolysis in up to 10% of the affected [3]. Several mechanisms are attributed to this deficiency. Ineffective erythropoiesis due to intramedullary destruction of red blood cells (RBC) is one of the mechanisms. Deficiency of vitamin B12 inhibits purine and thymidylate syntheses, which impairs DNA synthesis. This impairment of DNA synthesis causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis [4]. A deficiency of vitamin B12 can increase the precursors, including methylmalonic acid and Homocysteine. The accumulation of Homocysteine can increase hemolysis by oxidative damage and interaction with RBC structural and enzymatic proteins [5]. Homocysteine’s hemolytic action depends on a high ratio of PMNL to RBC, which was high in our patient [6].
A literature review of reporting of autoimmune hemolysis associated with DiGeorge syndrome (DS) using the search strategy of “((hemolysis) OR (hemolytic anemia)) AND (DiGeorge)” on PubMed yielded fifteen results. The literature consists of 8 case reports and a retrospective multicenter case-control study with 23 patients of 22q11.2 deletion syndrome (22q11.2DS) with hemolysis discussed the predictors for hematologic development autoimmunity (HA) [7-15] [Table 2].
Most of the cases describe AIHA associated with ITP or triple line cytopenia. To the best of our knowledge, 3 cases with AIHA as the sole autoimmune cell line involvement associated with DiGeorge syndrome are reported. This makes it the 4th reported case in the literature to the best of our knowledge. What makes this case unique is the single-cell line involvement and the late presentation. The other unique attribute of this case is vitamin B12 deficiency. The patient had a low normal vitamin B12 level, a normal thyroid function, a normal folate level, and was a non-alcohol user, with multi-lobulated neutrophils on the peripheral smear suggestive of vitamin B12 induced macrocytic anemia.