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.