Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VI. Inherited Disorders of RBCs
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protein 4.1 ( Smith et al. , 1983a ). Although the animal was
not anemic, the reticulocyte count was about twice normal
in compensation for a shortened RBC life span. This dog
was an offspring of a father-daughter mating. Both parents
had decreased band 4.1 and some elliptocytes.
Persistent marked elliptocytosis was recognized as an
incidental finding in a Labrador-chow crossbred dog ( Di
Terlizzi et al. , 2007 ). Occasional microspherocytes and rare
RBCs containing Hb crystals were also present. RBC membrane
mechanical stability and deformability were reduced.
Further analysis revealed a decreased ability of spectrin to
form tetramers because of a defect in β-spectrin.
3 . Hereditary Spherocytosis in Cattle
Severe hemolytic anemia with icterus and splenomegaly is
present shortly after birth in Japanese black cattle that lack
band 3 in their RBC membranes ( Inaba, 2000 ). The mortality
rate is high in affected animals, especially during the
first week of life. Those that survive exhibit persistent mild
hemolytic anemia (hematocrit 25% to 35%) with marked
spherocytosis and anisocytosis, but not reticulocytosis
(Inaba, 2000; Inaba et al. , 1996 ). Slight acidosis and growth
retardation are present. Affected RBCs also have reduced
amounts of other membrane proteins, including spectrin,
ankyrin, actin, and protein 4.2. RBCs exhibit defective
anion transport and a disrupted membrane skeletal network
that makes them extremely unstable. Spherocyte formation
results from a loss of surface area by invagination, vesiculation,
and extrusion of microvesicles, and fragmentation. This
defect is inherited as an autosomal dominant trait. RBCs
from carrier cattle that are heterozygous for this defect have
decreased band 3 (about 30% of normal), impaired anion
transport, and mild spherocytosis, but hematocrits are generally
normal. Osmotic fragility was increased in both heterozygous
and homozygous cattle. This defect demonstrates
the functional importance of the association of band 3 with
skeletal proteins in maintaining membrane stability.
4 . Hereditary Spectrin Defi ciency in Dogs with
Increased Osmotic Fragility
Increased RBC osmotic fragility secondary to spectrin deficiency
(50% to 70% of normal) has been reported as a common
autosomal dominant trait in golden retriever dogs in
the Netherlands ( Slappendel et al. , 2005 ). Hematocrits and
reticulocyte counts are within reference intervals. Although
originally reported as hereditary spherocytosis ( Slappendel,
1998 ), spherocytes are not recognizable on stained-blood
films. Rather, RBCs from affected dogs exhibited abundant
echinospherocytes after 24 h of incubation at room temperature.
In contrast, control dog RBCs exhibited only slight
echinocyte formation after incubation. The nature of the
spectrin defect has not been reported, but it is presumably
different from the β -spectrin defect described in a dog that
caused elliptocyte formation ( Di Terlizzi et al. , 2007 ).
5 . Hemolytic Anemia with Increased RBC Osmotic
Fragility in Cats
A hemolytic anemia with markedly increased osmotic
fragility has been reported in Abyssinian and Somali cats
( Kohn et al. , 2000 ). Splenomegaly and polyclonal hyperglobulinemia
were common. The hematocrit was generally
between 15% and 25%, but values as low as 5% were recognized.
A macrocytosis with mild to moderate reticulocytosis
was present in most cats. Most samples exhibited
extreme hemolysis after 1 day of refrigeration; however,
in vivo hemolysis also occurred, as evidenced by hemoglobinuria
in some cats. An RBC membrane defect was
suspected, but none was identified using conventional
membrane protein electrophoresis.
6 . Amino Acid Transport Defi ciency in Sheep
and Horses
A second type of GSH deficiency, inherited as an autosomal
recessive trait, occurs in Finnish Landrace sheep
( Tucker and Kilgour, 1970 ). Although affected animals are
not anemic, the life span of deficient RBCs is shortened
( Tucker, 1974 ), possibly from increased oxidant injury as
evidenced by the presence of HzB. These sheep are more
likely to become anemic following the administration of
oxidants in vivo ( Tucker et al. , 1981 ).
The amino acid transporter normally responsible for
cysteine transport (system C) into RBCs is defective ( Young
et al. , 1975 ), thereby limiting cysteine uptake and restricting
GSH synthesis. As a consequence, GSH concentrations
in RBCs are about 30% of normal ( Young et al. , 1975 ).
Intracellular Na and K are decreased, because dibasic
and other amino acids accumulate in this disorder ( Ellory
et al. , 1972 ). The transport deficiency appears to develop
during reticulocyte maturation, and intracellular amino
acids accumulating in these cells are believed to come from
protein degradation during reticulocyte maturation ( Tucker
and Young, 1980 ). When RBCs are separated by age, using
density gradients, intracellular GSH decreases and HzB
numbers increase in older RBCs from system C-deficient
sheep, but not from normal or GCS-deficient sheep ( Tucker
and Young, 1980 ). This decreasing GSH with RBC age may
explain why system C-deficient sheep are more susceptible
to oxidants than are GCS-deficient ones, even though they
have similar whole blood GSH levels.
About 30% of Thoroughbred horses and 3% of ponies
are deficient in a similar amino acid transporter. The lesion
results in increased amino acid levels and GSH deficiency
in some cases ( Fincham et al. , 1985 ).
7 . High Membrane Na ,K -ATPase Activity in Dogs
Although dog reticulocytes have considerable membrane
Na ,K -ATPase (Na ,K -pump) activity, it is rapidly lost