10-04-2006, 05:19 PM
17. A 14-year-old female complains to her pediatrician
of fatigue and occasional yellowish
discoloration to her skin. She has marked
splenomegaly. Laboratory studies are obtained:
Leukocytes = 3.4/mm3
Hematocrit = 30%
Hemoglobin = 9.6 g/dL
MCV = 90 fL
MCHC = 45%
Platelets = 250,000/uL
Peripheral smear demonstrates spherocytes.
Which of the following abnormal proteins is
most likely the cause of this patient™s signs and
symptoms?
(A) α-globin
(B) Ankyrin
© β-globin
(D) Protein 4.2
(E) Spectrin
(E) is correct. Hereditary spherocytosis is an autosomal
dominant disease characterized by a deficiency of
spectrin. This defect in the erythrocyte cell membrane
results in instability and increased osmotic fragility.
Clinically, there is jaundice, anemia, and
splenomegaly. Laboratories confirm the anemia and
demonstrate an increased mean corpuscular
hemoglobin.
Explanation A: No. Defects in α-globin result in the
α-thalassemias.
Explanation B: No. Ankyrin is an erythrocyte
membrane protein, but is not the etiology of hereditary
spherocytosis.
Explanation C: No. Defects in the β-globin result in
the β-thalassemias.
Explanation D: No. Protein 4.2 is an erythrocyte
membrane protein, but is not the etiology of hereditary
spherocytosis.
18. A 35-day-old infant is brought to the pediatrician
by her parents. Since discharge she has
not been feeding well and now seems lethargic.
The infant is dehydrated and hypotensive. She
has an enlarged clitoris. Serum electrolytes
demonstrate hyponatremia, hyperkalemia, and
hypoglycemia. Which of the following is the
most common cause of these findings?
(A) 3β-hydroxysteroid dehydrogenase
deficiency
(B) 11β-hydroxylase deficiency
© 17α-hydroxylase deficiency
(D) 21-hydroxylase deficiency
(E) Cholesterol side chain cleavage enzyme
deficiency
(D) is correct. 21-hydroxylase deficiency is the most
common cause of congenital adrenal hyperplasia, a
group of autosomal recessive inherited diseases in
which deficiency of corticosteroid hormones results in
the unregulated secretion of ACTH and thus adrenal
hyperplasia. In 21-hydroxylase deficiency, there is
often severe adrenal insufficiency with hyponatremia
and hyperkalemia due to the lack of aldosterone.
Females are also virilized; males appear normal.
Explanation A: No. 3β-hydroxysteroid dehydrogenase
deficiency is a rare cause of congential adrenal
hyperplasia, which also presents with adrenal
insufficiency and ambiguous genitalia in females.
Explanation B: No. 11β-hydroxylase deficiency results
in the accumulation of 11-deoxycortisol, a weak
mineralocorticoid with resultant sodium retention and
hypertension.
Explanation C: No. 17α-hydroxylase deficiency results
in hypokalemic alkalosis and hypertension.
Explanation E: No. Cholesterol side chain cleavage
enzyme deficiency results in almost no secretion of
cortisol, aldosterone, or sex steroids as this enzyme is
the rate-limiting step in generation of steroids. Infants
suffer severe adrenal insufficiency.
of fatigue and occasional yellowish
discoloration to her skin. She has marked
splenomegaly. Laboratory studies are obtained:
Leukocytes = 3.4/mm3
Hematocrit = 30%
Hemoglobin = 9.6 g/dL
MCV = 90 fL
MCHC = 45%
Platelets = 250,000/uL
Peripheral smear demonstrates spherocytes.
Which of the following abnormal proteins is
most likely the cause of this patient™s signs and
symptoms?
(A) α-globin
(B) Ankyrin
© β-globin
(D) Protein 4.2
(E) Spectrin
(E) is correct. Hereditary spherocytosis is an autosomal
dominant disease characterized by a deficiency of
spectrin. This defect in the erythrocyte cell membrane
results in instability and increased osmotic fragility.
Clinically, there is jaundice, anemia, and
splenomegaly. Laboratories confirm the anemia and
demonstrate an increased mean corpuscular
hemoglobin.
Explanation A: No. Defects in α-globin result in the
α-thalassemias.
Explanation B: No. Ankyrin is an erythrocyte
membrane protein, but is not the etiology of hereditary
spherocytosis.
Explanation C: No. Defects in the β-globin result in
the β-thalassemias.
Explanation D: No. Protein 4.2 is an erythrocyte
membrane protein, but is not the etiology of hereditary
spherocytosis.
18. A 35-day-old infant is brought to the pediatrician
by her parents. Since discharge she has
not been feeding well and now seems lethargic.
The infant is dehydrated and hypotensive. She
has an enlarged clitoris. Serum electrolytes
demonstrate hyponatremia, hyperkalemia, and
hypoglycemia. Which of the following is the
most common cause of these findings?
(A) 3β-hydroxysteroid dehydrogenase
deficiency
(B) 11β-hydroxylase deficiency
© 17α-hydroxylase deficiency
(D) 21-hydroxylase deficiency
(E) Cholesterol side chain cleavage enzyme
deficiency
(D) is correct. 21-hydroxylase deficiency is the most
common cause of congenital adrenal hyperplasia, a
group of autosomal recessive inherited diseases in
which deficiency of corticosteroid hormones results in
the unregulated secretion of ACTH and thus adrenal
hyperplasia. In 21-hydroxylase deficiency, there is
often severe adrenal insufficiency with hyponatremia
and hyperkalemia due to the lack of aldosterone.
Females are also virilized; males appear normal.
Explanation A: No. 3β-hydroxysteroid dehydrogenase
deficiency is a rare cause of congential adrenal
hyperplasia, which also presents with adrenal
insufficiency and ambiguous genitalia in females.
Explanation B: No. 11β-hydroxylase deficiency results
in the accumulation of 11-deoxycortisol, a weak
mineralocorticoid with resultant sodium retention and
hypertension.
Explanation C: No. 17α-hydroxylase deficiency results
in hypokalemic alkalosis and hypertension.
Explanation E: No. Cholesterol side chain cleavage
enzyme deficiency results in almost no secretion of
cortisol, aldosterone, or sex steroids as this enzyme is
the rate-limiting step in generation of steroids. Infants
suffer severe adrenal insufficiency.