CASE FILES: BIOCHEMISTRY
ANSWERS TO CASE 1: SICKLE CELL DISEASE
A 15-year-old African-American female with recurrent bilateral
thigh and hip pain, anemia, and symptoms and laboratory evidence of a urinary
Most likely diagnosis:
Sickle cell disease (pain crisis).
Biochemical mechanism of disease:
Single amino acid substitution on
hemoglobin beta chain, inherited in an autosomal recessive fashion (1 of
12 African Americans in United States are carriers of the trait).
Pathophysiologic mechanism of symptoms:
The sickled red blood
cells cause infarction of bone, lung, kidney, and other tissue from
This 15-year-old female’s description of her pain is typical of a sickle cell pain
crisis. Many times, infection is a trigger, most commonly pneumonia or a urinary
tract infection. This case is consistent with a urinary tract infection, indicated by
her symptoms of urinary frequency, and burning with urination (dysuria). Her
white blood cell count is elevated in response to the infection. The low hemo-
globin level is consistent with sickle cell anemia. Since she is homozygous
(both genes coding for sickle hemoglobin), both her parents have sickle cell
trait (heterozygous) and thus do not have symptoms. The diagnosis can be
established with hemoglobin electrophoresis. Treatment includes searching for
an underlying cause of crisis (infection, hypoxia, fever, excessive exercise, and
extreme changes in temperature), administration of oxygen, intravenous fluids
for hydration, pain management, and consideration of a blood transfusion.
APPROACH TO SICKLE CELL DISEASE
Understand the primary, secondary, tertiary, and quaternary levels of
Be able to describe the structure of hemoglobin and its role in oxygen
binding and dissociation.
Be able to describe the mechanism that amino acid substitution results
in sickle cell hemoglobin.