Pathophysiology of Disease: An Introduction to
Clinical Medicine
8th Edition
Author(s)Gary D. Hammer; Stephen J. McPhee
TEST BANK
1
Reference — Ch. 2 — Genetic Disease
Question Stem
A 3-year-old boy with consanguineous parents presents with
recurrent infections and failure to thrive. You suspect an
autosomal recessive immunodeficiency. Which element of the
family history most increases the posterior probability that this
is an autosomal recessive condition?
A. Multiple affected males across two generations
B. Affected siblings with unaffected parents
,C. Maternal transmission only across generations
D. Early onset disease in multiple heterozygous adults
Correct Answer: B
Rationales
• Correct (B): Autosomal recessive disorders often present in
siblings born to unaffected carrier parents; consanguinity
increases the chance both parents carry the same
recessive allele.
• A: Multiple affected males across generations suggests X-
linked inheritance, not classic autosomal recessive.
• C: Maternal-only transmission points toward mitochondrial
inheritance, not autosomal recessive.
• D: Heterozygous adults are usually carriers with little or no
early onset disease in autosomal recessive conditions.
Teaching Point
Affected siblings with unaffected parents suggest autosomal
recessive inheritance.
Citation (Simplified APA)
Hammer & McPhee (2019). Pathophysiology of Disease (8th
Ed.). Ch. 2.
2
Reference — Ch. 2 — Genetic Disease
,Question Stem
Newborn screening returns a markedly elevated phenylalanine
level. Which pathophysiologic mechanism best explains the risk
for intellectual disability if untreated?
A. Phenylalanine competitively inhibits transport of other large
neutral amino acids into the brain.
B. Phenylalanine directly hyperstimulates oligodendrocytes
increasing myelination.
C. Excess phenylalanine causes hypoglycemia and neuronal
starvation.
D. Phenylalanine forms insoluble deposits in cortical capillaries.
Correct Answer: A
Rationales
• Correct (A): High phenylalanine levels competitively block
transport of other large neutral amino acids across the
blood–brain barrier, impairing neurotransmitter synthesis
and brain development.
• B: Excess phenylalanine does not increase myelination; it
impairs normal brain development.
• C: Phenylketonuria does not cause hypoglycemia as the
primary mechanism of neurologic injury.
• D: Phenylalanine does not cause insoluble cortical capillary
deposits as the mechanism of damage.
, Teaching Point
Elevated phenylalanine impairs brain amino acid transport and
neurotransmitter synthesis.
Citation (Simplified APA)
Hammer & McPhee (2019). Pathophysiology of Disease (8th
Ed.). Ch. 2.
3
Reference — Ch. 2 — Genetic Disease
Question Stem
A woman is heterozygous for an X-linked recessive disorder. She
asks why some heterozygous females show disease while others
do not. Which genetic concept best explains variable expression
in heterozygous females?
A. Skewed X-chromosome inactivation (lyonization) producing
functional hemizygosity in some tissues
B. Mitochondrial heteroplasmy transmitted through the mother
C. Anticipation due to trinucleotide repeat expansion
D. Autosomal recessive carrier frequency differences
Correct Answer: A
Rationales
• Correct (A): Random X inactivation can be skewed so a
higher proportion of cells express the X chromosome
Clinical Medicine
8th Edition
Author(s)Gary D. Hammer; Stephen J. McPhee
TEST BANK
1
Reference — Ch. 2 — Genetic Disease
Question Stem
A 3-year-old boy with consanguineous parents presents with
recurrent infections and failure to thrive. You suspect an
autosomal recessive immunodeficiency. Which element of the
family history most increases the posterior probability that this
is an autosomal recessive condition?
A. Multiple affected males across two generations
B. Affected siblings with unaffected parents
,C. Maternal transmission only across generations
D. Early onset disease in multiple heterozygous adults
Correct Answer: B
Rationales
• Correct (B): Autosomal recessive disorders often present in
siblings born to unaffected carrier parents; consanguinity
increases the chance both parents carry the same
recessive allele.
• A: Multiple affected males across generations suggests X-
linked inheritance, not classic autosomal recessive.
• C: Maternal-only transmission points toward mitochondrial
inheritance, not autosomal recessive.
• D: Heterozygous adults are usually carriers with little or no
early onset disease in autosomal recessive conditions.
Teaching Point
Affected siblings with unaffected parents suggest autosomal
recessive inheritance.
Citation (Simplified APA)
Hammer & McPhee (2019). Pathophysiology of Disease (8th
Ed.). Ch. 2.
2
Reference — Ch. 2 — Genetic Disease
,Question Stem
Newborn screening returns a markedly elevated phenylalanine
level. Which pathophysiologic mechanism best explains the risk
for intellectual disability if untreated?
A. Phenylalanine competitively inhibits transport of other large
neutral amino acids into the brain.
B. Phenylalanine directly hyperstimulates oligodendrocytes
increasing myelination.
C. Excess phenylalanine causes hypoglycemia and neuronal
starvation.
D. Phenylalanine forms insoluble deposits in cortical capillaries.
Correct Answer: A
Rationales
• Correct (A): High phenylalanine levels competitively block
transport of other large neutral amino acids across the
blood–brain barrier, impairing neurotransmitter synthesis
and brain development.
• B: Excess phenylalanine does not increase myelination; it
impairs normal brain development.
• C: Phenylketonuria does not cause hypoglycemia as the
primary mechanism of neurologic injury.
• D: Phenylalanine does not cause insoluble cortical capillary
deposits as the mechanism of damage.
, Teaching Point
Elevated phenylalanine impairs brain amino acid transport and
neurotransmitter synthesis.
Citation (Simplified APA)
Hammer & McPhee (2019). Pathophysiology of Disease (8th
Ed.). Ch. 2.
3
Reference — Ch. 2 — Genetic Disease
Question Stem
A woman is heterozygous for an X-linked recessive disorder. She
asks why some heterozygous females show disease while others
do not. Which genetic concept best explains variable expression
in heterozygous females?
A. Skewed X-chromosome inactivation (lyonization) producing
functional hemizygosity in some tissues
B. Mitochondrial heteroplasmy transmitted through the mother
C. Anticipation due to trinucleotide repeat expansion
D. Autosomal recessive carrier frequency differences
Correct Answer: A
Rationales
• Correct (A): Random X inactivation can be skewed so a
higher proportion of cells express the X chromosome
