Case Report

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Bombay and Lewis Phenotype Testing
in Correlation with Leukocyte Adhesion
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Deficiency Type II: The Blood Bank’s

Role in Diagnosis
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Website:
[Link] Khalid Batarfi, Ahmed Maded Al Harbi, Bryan Rosario, Abdullah Al Enazi,
DOI:
Paolo Domingo Kiseo
10.4103/joah.joah_85_19

Abstract:
Leukocyte adhesion deficiency type II (LAD II) is a rare hereditary disorder caused by the mutation
in the guanosine diphosphate‑fucose transporter gene (SLC35C1). LAD II is characterized by
inexpression of ABO antigens (i.e., Bombay phenotype) and the lack of Lewis red blood cell (RBC)
antigens. In addition to high neutrophil counts, patients also manifest recurrent infections with
developmental delays and stunted growth. Blood bank laboratory tests such as blood grouping, RBC
phenotyping, antibody screening and identification of the nature of the antibody were conducted
in order to confirm the consequences associated with this gene anomaly in this case report. Type
and screen results initially identified the patient as group “O” Rh positive with pan‑reactive antibody
screening cells and identification panel cells. The patient plasma showed significant incompatibility
to all O‑positive donors’ RBCs. The patient’s RBCs were tested against anti‑H lectin and Lewis (Lea,
Leb) typing antisera and showed no reaction, which meant that the patient does not express neither
Lewis antigens nor H antigen on his red cell. The presence of anti‑H (in a Bombay phenotype
individual) explained the reactivity to reagent red cells and crossmatched incompatibility of Group
O units as these cells naturally contained the H antigen.
Keywords:
Bombay blood group, fucose synthesis, leukocyte adhesion deficiency Type II, Lewis phenotype

Introduction adhesion resulting in ineffective chemotaxis,

which leads to the inability to form pus

Department of Pathology
and Laboratory Medicine,
L eukocyte adhesion deficiency (LAD) is a
very rare autosomal recessive condition
which was first observed during the 1980s.[1]
and very high WBC counts (leukocytosis,
neutrophillia).[3] It is a syndrome wherein
leukocytes are unable to adhere and migrate
King Abdullah Specialist
Children Hospital, King This practically new and uncommon disease during inflammatory processes and defense
Abdulaziz Medical had only been defined in the 1990s, and only reactions. Normally, leukocytes move
City‑CR, Ministry of less than 10 cases had been described since its through the bloodstream and “roll” along
National Guard, Riyadh, discovery. Remarkably, this disease is only the endothelial wall and travel to target
Saudi Arabia
presented with an equally rare blood group: sites along the surrounding tissue, and these
Address for the Bombay phenotype. Lewis antigens movements are regulated through primary
correspondence: are also inexpressed as these blood group adhesive integrin receptors.[4] There are three
Mr. Ahmed Maded Al Harbi, systems rely on effective fucose synthesis.[2] types to this condition (LAD I, II, and III)
Department of Pathology
As a distinct clinical manifestation, patients depending on the defective integrin. LAD II,
and Laboratory Medicine,
King Abdullah Specialist experience recurrent bacterial infections on the other hand, is the rarest, with less than
Children Hospital, King due to a defective White Blood Cell (WBC) ten patients being described. It is a milder
Abdulaziz Medical City‑CR, form of the disease which has a compromised
Ministry of National Guard,
fucosyltransferase activity caused by loss of
Riyadh, Saudi Arabia. This is an open access journal, and articles are
E‑mail: Harbiah1@ngha. distributed under the terms of the Creative Commons
[Link] Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows How to cite this article: Batarfi K, Al Harbi AM,
others to remix, tweak, and build upon the work non‑commercially, Rosario B, Al Enazi A, Kiseo PD. Bombay and Lewis
Submitted: 12‑Dec‑2019 as long as appropriate credit is given and the new creations are phenotype testing in correlation with leukocyte
Revised: 23-Feb-2020 licensed under the identical terms. adhesion deficiency type II: The blood bank's role in
Accepted: 05‑Jun‑2020 diagnosis. J Appl Hematol 2020;11:132-4.
Published: 16-Sep-2020 For reprints contact: WKHLRPMedknow_reprints@[Link]

132 © 2020 Journal of Applied Hematology | Published by Wolters Kluwer - Medknow

 Batarfi, et al.: LAD II with Bombay and lewis phenotype

fucose synthesis.[2] This leads to the nonexpression of the H gene result in congenital disorders of glycosylation type
antigens, ABO, and Lewis blood group antigens and poor IIc leading to leukocytosis and recurrent infections.
formation of Sialyl‑Lewisx, an L‑selectin ligand necessary Hence, these findings confirmed that this patient blood
for cellular movement and chemotaxis. Only in LAD II, group is Bombay blood group.
since the disease process involves the inability to properly
synthesize fucose, results in the inexpression of ABH and Discussion
Lewis blood group antigens that could be observed using
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routine blood banking techniques.[5] The ABO blood group system is unique in such a way
that antibodies will be produced naturally against the
Case Report lacking antigen on red cells. ABO typing is done by
forward grouping, accompanied by a reverse typing
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A 13 months old Saudi boy was referred to the pediatric to confirm this activity. Routine typing would include
cardiology clinic at King Abdulaziz Medical City in testing the cells with A, B, and D (Rh) antisera on the
Riyadh. He was diagnosed with severe peripheral forward, and testing the plasma with reagent A1 cells
pulmonary stenosis with moderate chronic pericardial and B cells, but further investigation with H lectin was
effusion. Other significant medical histories and needed in this case to investigate the strong antibody
clinical observations include slight prematurity at reaction where no compatible RBC unit was found. The
birth (i.e., 35th week) with low birth weight (1.8 kg), mental antibody screening and identification gave clues about
retardation, facial dysmorphic features (depressed nasal the possible immunoglobulin (reacts best in cold and
bridge), hypospadias, and fever of unknown origin with room temperature while IgG reacts at 37°C) present
high WBC count (leukocytosis an average of 35–50 × 109 but could not rule out the definite antibody due to their
L). The medical team’s initial assessment and planning panreactivity patterns. A simple procedure of testing the
were urgent medical evaluation and further workup patient’s cell with anti‑H and his plasma against a panel
for immediate cardiac catheterization and open‑heart of RBC with different ABO groups demonstrated that the
surgery. Tests were conducted including basic ABO/Rh patient lacked the H antigen one his RBCs and has anti‑H
typing and antibody screening (T/S), and the patient was in his plasma, which confirms the Bombay phenotype.
typed as Group O positive with a pan‑reactive antibody In addition, the Lewis blood group typing results of the
screening. As a next step, antihuman globulin antibody patient were found to be Le (a−b−). These results highly
identification and direct antiglobulin test (DAT) were suggest the patient’s suspected fucosylation deficiency,
done using solid‑phase technique. The patient’s plasma which can be related in this case to LAD II, where
was positive to all antibody identification panel cells with patients are unable to express H and Lewis antigens.
a negative DAT result, which was at the time interpreted The addition of the sugars N-acetylgalactosamine and
as probable clinically significant IgG alloantibody to a D-galactose to the H structure results in the formation
high‑incidence antigen of unknown identity. Efforts of the A and B antigens respectively. In the absence of
were made to find compatible O‑positive packed the H antigen, these reactions cannot take place. Thus,
red blood cell (RBC) units for the surgery, but none the A and B antigens are not produced even if the A and
within the inventory could be found using a complete B genes are present. People who lack the A, B, and H
crossmatch as the compatibility testing showed strong antigens in their blood produce anti‑A, anti‑B, and anti‑H
reactivity and significant incompatibility. Surgery had antibodies as a consequence. The absence of A and B
to be, therefore, canceled, and all orders for transfusion antigens mimics the O blood group, but the presence of
were put on hold. Further investigation was performed the anti‑H antibody causes a cross‑reaction with all blood
where the patient’s RBCs were tested against anti‑H, types, including the O group blood, which carries the H
and it was negative in addition to that the patient’s antigen.[6] Despite its rarity, the clinical significance of
plasma was tested against A1 cells, A2 cells, B cells, this condition must not be underestimated due to its role
and O cells and displayed strong agglutination (4+); in causing transfusion reactions.[7] If recurrent infections,
this patient lacks the H antigen on the RBCs which persistent hyperleukocytosis, and severe mental and
accompanied by the presence of anti‑H antibody in his growth retardation are present in an individual with the
plasma. Moreover, there was no agglutination in the Bombay blood group, we should consider the possibility
autocontrol test (a mixture of the patient’s cells and of the rare diagnosis of LAD II.[8]
plasma). This means that the patient will be compatible
with only Bombay blood group donor. In addition to the Conclusion
blood bank testing, a genetic study was conducted and
the patient was found to be homozygous for a variant The malfunction in the patient’s SLC35C1 gene assumably
p.Thr295IIe in the SLC35C1 gene. This gene encodes a prohibited the transport of GDP‑fucose to be synthesized
Guanine diphosphate-fucose (GDP-fucose) transporter into its functional form. This prevented a cascade of
that is found in the Golgi apparatus. Mutations in this activities, wherein fucosylation – an action necessary for
Journal of Applied Hematology - Volume 11, Issue 3, July - September 2020 133
 Batarfi, et al.: LAD II with Bombay and lewis phenotype

brain development, red cell antigenicity, and leukocyte Conflicts of interest

function – was not possible. Neutrophil inactivity, There are no conflicts of interest.
the absence of Lewis antigens plus the occurrence
of the Bombay phenotype are all consequences of References
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Nil. Eur J Immunol 2019;44:206‑9.

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