1. Art and Diseño

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CORRESPONDENCE
1656
Southeast Asian Ovalocytosis in a South African Kindred With Hemolytic Anemia
To the Editor:
Southeast Asian ovalocytosis (SAO) isa dominantly inherited disorder that is widespread in certain ethnic groups of Malaysia, Indonesia,
Papua New Guinea, and the Philippines.’,2
SA0 red blood cells (RBCs)
areovalocyticinshape,rigid,andresistanttoinvasion
by different
strains of malaria parasites.’l’ MembranesSA0
of RBCs do not undergo
salt-induced crenation,’ and several blood group antigens, but not the
Affected hetemGerbich antigens, havea reduced level of expression?
zygous individuals are asymptomatic, with no clinically detectable hemolysis,’ although one subject has been described with compensated
hemolysis.’ The homozygous state has been postulated to be lethal?
The underlying moleculardefect in SA0 is a deletion of 27 bp in the
band 3 gene resulting in the absence of 9 amino acids at the boundary
of the cytoplasmic and membrane domains of band 3.9”’ This defect
is tightly linked in all casesof SA0 to the band 3 Memphis I polymorglu substitution?The
phism, a pointmutationcausing a lys56
prevalence of SA0 in other population groups is not known, but one
Mauritian subjectof Indian extraction and oneAfrican-American family
have been repo~ted.’,’’
We now describe the first instance of dominantly inherited
SA0
in a four-generation South African Cape Colored familythatalso
showed two additional unusual features. Firstly, all affected subjects
exhibited varying degrees of hemolytic anemia. Secondly, the band
3 Memphis I polymorphism was not linked to SA0
the band 3 deletion
in all subjects.The family members studied consisted of seven affected
and three normal individuals. Clinically, all affected subjects showed
evidence of hemolysis, ranging from a severe transfusion-dependant
conditiontocompensatedhemolysis.
One individualcontinuedto
hemolyse after splenectomy.Other causes of hemolysis, such as hemoglobinopathies or enzyme deficiencies,wereruled out. RBCs from
affected individuals showed the characteristic spoon-shaped stomatocytic ovalocytic morphology and incubation of SA0 RBC ghosts in
isotonic saline did not alter themorphology,incontrasttocontrol
ghosts that becamesmaller and echinocytic. In vitro infection ofSA0
and normal RBCs withPlasmodium falciparum and culturing for two
cycles of parasite invasion and growth showed a markedly decreased
level of parasitemia in SA0 cells. Several blood group antigens, including the Gerbich antigens, were depressed.
Polymerase chain reaction (PCR) amplification of genomic DNA
using primers flanking the S A 0 deletion in exon 11 of the band 3
gene showed two products of 175 and 148 bp, indicating that the
affected individuals were heterozygous for the 27-bp S A 0 band 3
gene deletion. Normal family members only showed amplification
of the 175-bp fragment. The presence of theband 3 Memphis I
polymorphism was analyzed by limited tryptic digestion of RBC
ghosts followed by electrophoresis and immunoblotting with an antiband 3 antibody. The protein findings were confirmed by PCR amplification of the band 3 gene and DNA sequencing. Interestingly, six
S A 0 subjects and all three normal family members were heterozygous for the band 3 Memphis I polymorphism (Lys 56 Glu) and
one S A 0 subject was homozygous.
The Cape Coloreds are a hybrid people into whose ancestry a
Caucasoid element has entered. The other element is usually of
African origin (Khoi, San, or Negro), butmay also be the hybrid
Caucasoids from Malaysia or India.I3The origin of this Cape Colored
family is not known, but we speculate that the SA0 gene was introduced into the family ancestors during the 17th or 18th century by
a Malaysian or Indonesian forebear who came to the Cape Town
settlement with the Dutch East India Company. Alternatively, the
SA0 gene deletion could have arisen independently in this family.
This may be less likely because it is a relatively large deletion (27
+
+
bp) and, in addition, the Cape region of South Africa is notan
endemic malaria area. It has been postulated that the S A 0 mutation
is an ancient one probably selected for by the protection the gene
affords against malaria.2,3
In summary, our results indicate that the S A 0 phenotype also
occurs in the South African Cape Colored population and is not
always clinically asymptomatic. Furthermore, the inheritance of the
band 3 Memphis I polymorphism in an affected family is not necessarily indicative of SAO.
T.L Coetzer
L. Beeton
D. van Zyl
S.P. Field
Department of Haematology
School of Pathology
University of the Witwatersrand
South African Institute for Medical Research
Johannesburg, South Africa
A. Agherdien
Port Elizabeth, South Africa
E. Smart
Natal Blood Transfusion Service
Durban, South Africa
G.L. Daniels
MRC Blood Group Unit
University College London
London, UK
REFERENCES
1. Amato D, Booth PB: Hereditary ovalocytosis in Melanesians.
PNG Med J 20:26, 1977
2. Nurse GT, Coetzer TL, Palek J: The elliptocytoses, ovalocytosis and related disorders. Clin Haematol 5:187, 1992
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hereditary ovalocytosis. Hum Genet 137:161, 1977
4. Kidson C, Lamont G, Saul A, Nurse GT: Ovalocytic erythrocytes from Melanesians are resistant to invasion by malaria parasites
in culture. Roc Natl Acad Sci USA 785829, 1981
5. Liu S-C, Zhai S, Palek J, Golan DE, Amato D, Hassan K,
Nurse GT, Babona D, Coetzer T, Jarolim P, Zaik M, Borwein S:
Molecular defect of the band 3 protein in Southeast Asian Ovalocytosis. N Engl J Med 323:1530, 1990
6. Booth PB, Serjeantson S , Woodfield DG, Amato D: Selective
depresson of blood groups antigens associated with hereditary ovalocytosis among Melanesians. Vox Sang 32:99, 1977
7. Reardon DM, Seymour CA, Cox TM, Pinder JC, Schofield
AE, Tanner MJA: Hereditary ovalocytosis with compensated haemolysis. Br J Haematol 85:197, 1993
8. Liu S-C, Jarolim P, Rubin HL, Palek J: The homozygous state
for the band 3 protein mutation in Southeast Asian ovalocytosis may
be lethal. Blood 84:3590, 1994
9. Jarolim P, Palek J, Amato D, Hassan K, Sapak P, Nurse GT,
Rubin HL, Zhai S, Sahr KE, Liu S-C: Deletion in erythrocyte band
3 gene in malaria-resistant Southeast Asian ovalocytosis. Proc Natl
Acad Sci USA 88:11022, 1991
10. Tanner MJA, Bruce L, Martin PG, Rearden DM, Jones GL:
Melanesian hereditary ovalocytes have a deletion in red cell band
3. Blood 78:2785, 1991
11. Mohandas N, Winardi R, Knowles D, Leung A, Parra M,
George E, Conboy J, Chasis J: Molecular basis for membrane rigidity
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From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
CORRESPONDENCE
12. Ravindranath Y, Goyette G, Johnson RM: Southeast Asian
ovalocytosis in an African-American family. Blood 84:2821,
1995
1657
13. Nurse GT, Weiner JS, Jenkins T: The growth of hybrid communities, in The Peoples of Southern Africa and Their Affinities.
Oxford, UK, Oxford Clarendon, 1985, p 218
From www.bloodjournal.org by guest on February 6, 2015. For personal use only.
1996 87: 1656-1657
Southeast Asian ovalocytosis in a South African kindred with
hemolytic anemia [letter]
TL Coetzer, L Beeton, D van Zyl, SP Field, A Agherdien, E Smart and GL Daniels
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