Clinical Pathology(Molecular)

Front 1

Which of the following most closely phenotypically resembles Turner syndrome?
A. Patau syndrome
B. Edward syndrome
C. Down syndrome
D. Noonan syndrome
E. Klinefelter syndrome

Back 1

D. Noonan syndrome.
Superficially, both Noonan and Turner syndromes appear similar - wide-spaced nipples, webbed neck, and short stature. Noonan syndrome is autosomal dominant and
linked to mutations in the genes PTPN11 on chromosome 12q and KRAS on 12p.
QCCP2, Noonan syndrome.

Front 2

What are the two causes of Prader-Willi syndrome (pick 2)?
A. microdeletion in paternal 15q11.2
B. microdeletion in maternal 15q11.2
C. uniparental (maternal) disomy
D. uniparental (paternal) disomy
E. methylation of maternal 15q11.2

Back 2

A. microdeletion in paternal 15q11.2.
C. uniparental (maternal) disomy.
Prader-Willi and Angelman syndrome are genotypically, though not phenotypically, related entities caused by microdeletions or inactivations in the same region of
chromosome 15q11.2. The difference is that Prader-Willi is due to a loss of paternal activity and Angelman is due to a loss of maternal activity (“Daddy's little angel”).
Therefore, loss of parental DNA leads to Prader-Willi.
QCCP2, Angelman syndrome and Prader-Willi syndrome.

Front 3

All of the following are examples of trinucleotide repeat expansions, except:
A. Huntington disease
B. Bloom syndrome
C. Fragile X syndrome
D. Friedreich ataxia
E. all of the above are examples of trinucleotide repeat expansions

Back 3

B. Bloom syndrome.
Huntington disease is a CAG repeat disorder, Fragile X is a CGG repeat disorder, Friedreich ataxia is a GAA repeat disorder. For each of these disorders, the expansion
leads to chromosome instability in vitro. The in vivo effect of expansion may be due to increased silencing of the involved gene secondary to increased methylation. Of
the three disorders, only Friedreich ataxia does not exhibit anticipation!
QCCP2, Friedreich ataxia.

Front 4

All of the following disorders demonstrate increased sensitivity to ionizing radiation, except:
A. Friedreich ataxia
B. xeroderma pigmentosa
C. ataxia telangiectasia
D. Bloom syndrome
E. all of the above demonstrate increased sensitivity to ionizing radiation

Back 4

A. Friedreich ataxia.
Both xeroderma pigmentosa and Bloom syndrome patients are at risk for cutaneous neoplasms in sun-exposed skin, while patients with ataxia telangiectasia are
subject to ionizing radiation and develop hematolymphoid malignancies.
QCCP2, Friedreich ataxia, xeroderma pigmentosa, Bloom syndrome, ataxia telangiectasia.

Front 5

Which of the following syndromes is most consistent with aplastic anemia and absent radii?
A. xeroderma pigmentosa
B. Fanconi anemia
C. Nijmegen breakage syndrome
D. Bloom syndrome
E. ataxia telangiectasia

Back 5

B. Fanconi anemia.
Among the distinctive features of Fanconi anemia, aplastic anemia and forearm malformations, there is also short stature, café au lait spots, an increased risk of
malignancy, ocular and renal anomalies, and sensorineural hearing loss. Multiple genes are involved and the cytogenetic assay shows increased chromosome breakage.
QCCP2, Fanconi anemia.

Front 6

True or false: Mitochondrial disease is due exclusively to mutations in mitochondrial DNA.

Back 6

False.
While mitochondrial disease is due to mutations in mitochondrial proteins, not all mitochondrial proteins are encoded by mitochondrial genes. There are a significant
number of mitochondrial proteins that are encoded by nuclear genes.
QCCP2, Mitochondrial disease.

Front 7

Which of the following accounts for the clinical variability of mitochondrial disease?
A. homoplasmy
B. heteroplasmy
C. nuclear genes, exclusively
D. mitochondrial membrane thickness
E. gender

Back 7

B. heteroplasmy.
A cell will typically contain a single clonal population of mitochondria, a state known as homoplasmy. Cells affected by mitochondrial disease may contain more than one
clone, a condition called heteroplasmy. Variations in the population of normal mitochondria and abnormal mitochondria may account for the differences.
QCCP2, Mitochondrial disease.

Front 8

All of the following are examples of mitochondrial disease, except:
A. Kearns-Sayre syndrome
B. mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS)
C. myoclonic epilepsy with ragged red fibers (MERRF)
D. Leber hereditary optic neuropathy
E. Nijmegen breakage syndrome

Back 8

E. Nijmegen breakage syndrome.
Mitochondrial disease tends to manifest at an early age, childhood to early adulthood with the mutations in nuclear genes presenting earliest, mitochondrial genes later.
There is usually neuromuscular involvement. The typical muscle biopsy feature is the “ragged red fiber” seen on Gomori trichrome staining.
QCCP2, Nijmegen breakage syndrome, Mitochondrial disease.

Front 9

Which of the following features do organic acidemias and urea cycle disorders have in common?
A. autosomal recessive inheritance
B. hyperammonemia
C. typically normal appearance at birth
D. A & B
E. A, B, C

Back 9

E. A, B, C.There are number of diseases lumped under the rubric “organic acidemias,” such as maple syrup urine disease and the urea cycle disorders. They are all autosomal
recessive disorders that share hyperammonemia in common. As ammonia accumulates, symptoms such as vomiting, lethargy, and neurological deterioration appear.
QCCP2, Organic acidemias and urea cycle disorders.

Front 10

Which of the following is NOT a sphingolipidosis?
A. Gaucher disease
B. Hurler disease
C. Niemann-Pick disease
D. Fabry disease
E. Tay-Sachs disease

Back 10

B. Hurler disease.
Hurler and Hunter disease are mucopolysaccharidoses, characterized by the accumulation of mucopolysaccharides, such as dermatan, heparan, keratan, or chondroitin
sulfate. The accumulations can occur in a number of places, especially the spleen, liver, heart, and brain. This sphingolipidoses have accumulations of glycolipids, such
as sphingomyelin, gangliosides, or glucocerebrosides.
QCCP2, Inherited Metabolic Disorders T7.10.

Front 11

In which of the following disorders does the affected individual exhibit self-mutilating behavior, such as finger/lip-biting and head banging?
A. Krabbe disease
B. Fabry disease
C. Lesch-Nyhan disease
D. Hunter disease
E. cystinosis

Back 11

C. Lesch-Nyhan disease.
A fairly memorable presentation, Lesch-Nyhan is due to hyperuricemia as a result of a defect in the X-linked gene, hypoxanthine guanine phosphoribosyl transferase
(HGPRT). HGPRT is a critical enzyme in the purine salvage biosynthetic pathway. A deficiency of HGPRT leads to overproduction of urate.
QCCP2, Lesch-Nyhan syndrome.

Front 12

Deficiency of which of the following enzymes is associated with angiokeratomas and blindness?
A. hypoxanthine guanine phosphoribosyl transferase (HGPRT)
B. galactocerebrosidase
C. phenylalanine hydroxylase
D. alpha-galactosidase
E. galactose-1-phosphate uridyl transferase

Back 12

D. alpha-galactosidase.
Fabry disease is an X-linked recessive condition caused by a mutation in the gene encoding alpha-galactosidase. The manifestations of the disease include distal
extremity pain, angiokeratomas, hypohydrosis, corneal opacities, renal failure, cardiovascular or cerebrovascular disease, all due to accumulation of
globotriaosylceramide.
QCCP2, Fabry disease.

Front 13

Which of the following metabolic disorders presents with characteristic hexagonal and birefringent crystals deposited in the cornea, bone marrow, and kidney?
A. cystinuria
B. alkaptonuria
C. maple syrup urine disease
D. Krabbe disease
E. none of the above

Back 13

A. cystinuria.
The characteristic crystals of cystinuria are not only evident in the urine but can also be often visualized by slit lamp illumination of the cornea. The CTNS gene on
chromosome 17p13 is mutated in cystinuria.
QCCP2, Cystinosis.

Front 14

Which of the following is the most common chromosome abnormality in LIVE births?
A. monosomy X
B. triploidy
C. trisomy 16
D. trisomy 21
E. trisomy 18

Back 14

D. trisomy 21.
Monosomy X (45, X or Turner syndrome), triploidy, and trisomy 16 are more commonly associated with spontaneous abortions (especially trisomy 16, which is the most
common mutation seen in spontaneous abortions). Trisomy 18 causes Edwards syndrome and is associated with live births, but is nowhere nearly as common as
trisomy 21.
QCCP2, Structural and numerical chromosomal disorders.

Front 15

Which population demographic accounts for the majority of parentage of Down syndrome offspring?
A. fathers >25 years old
B. fathers >35 years old
C. mothers <35 years old
D. mothers >35 years old
E. there is no age preference

Back 15

B. mothers <35 years old.
A little tricky, I admit. While the risk of Down syndrome increases with maternal age from 1/725 for a 32 year-old mother to 1/365 for a 35 year-old mother, a greater
number of children are born to women less than 35 years old. As a matter of fact, more than 80% of cases of Down syndrome are in babies born to women less than
35 years old. Paternal age as a risk factor for Down syndrome is controversial, with some large studies showing no correlation while a few small studies have shown a
significant effect.
QCCP2, Down syndrome.

Front 16

What is the most common outcome of monosomy X?
A. spontaneous abortion
B. Turner syndrome
C. Edward syndrome
D. Down syndrome
E. Patau syndrome

Back 16

A. spontaneous abortion.
45, X is one of the most common abnormalities in spontaneous abortions, with 99% of 45, X conceptuses spontaneously aborting. Those that do live are affected by
Turner syndrome and usually live to adulthood.
QCCP2, Turner syndrome.

Front 17

What are the two most critical times for the regulation of phenylalanine intake in order to minimize morbidity (pick 2)?
A. infancy
B. early childhood
C. early adulthood
D. pregnancy
E. menopause/later adulthood

Back 17

B. early childhood.
D. pregnancy.
The morbidities associated with elevated phenylalanine include mental retardation and seizures. Removing phenylalanine from the diet of very young affected children
can ameliorate many of the sequelae. After early childhood, tight phenylalanine control is not as critical. There is one notable exception - the offspring of affected
pregnant women with poor control can be subject to a number of problems, even if the child is not phenylalanine hydroxylase deficient.
QCCP2, Phenylketonuria (PKU).

Front 18

Which one of the following infections are children with galactosemia at the highest risk of contracting?
A. cryptococcal meningitis
B. E. coli sepsis
C. Burkholderia pneumonia
D. subacute bacterial endocarditis
E. Actinomyces cervicitis

Back 18

B. E. sepsis.
Especially in the neonatal period, children with galactosemia are at a higher than normal risk for E. coli sepsis. Some of the other infections mentioned in the question
are associated with other predisposing conditions - cryptococcal meningitis is a common opportunistic infection in patients with AIDS, Burkholderia pneumonia is most
commonly seen in patients with cystic fibrosis, subacute bacterial endocarditis is seen in patients with damaged heart valves or patients with high levels of bacteremia,
and finally, Actinomyces cervicitis is most commonly associated with IUD use.
QCCP2, Galactosemia.

Front 19

What is the enzyme deficient in Tay-Sachs disease?
A. galactose-1-phosphate uridyl transferase
B. tay-saccharidase I
C. glycosphingolipid
D. hexosaminidase A
E. glucocerebrosidase

Back 19

D. hexosaminidase A.
Choice A is the enzyme deficient in galactosemia (GALacTosemia), while E is deficient in Gaucher disease. In patients affected by Tay-Sachs, glycosphingolipids
accumulate in the lysosomes. Choice B, Tay-saccharidase I is something I made up because I like the sound of it. One way to remember that hexosaminidase is
deficient in Tay-Sachs is to pronounce the disease, “Tay-Sex” (sex = hex).
QCCP2, Tay-Sachs disease (GM2 gangliosidosis).

Front 20

All of the following syndromes are associated with accumulations of very long chain fatty acids (VLFCA), except:
A. Gaucher disease
B. classic Zellweger syndrome
C. neonatal adrenoleukodystrophy
D. infantile Refsum disease
E. all of the above are VLCFA diseases

Back 20

A. Gaucher disease.
Classic Zellweger with the dysmorphic features and multiple biochemical anomalies presents earlier than neonatal adrenoleukodystrophy or Refsum disease and is
more severe. The characteristic facial features of Zellweger (flattened facies with large fontanelle and broad nasal bridge) are also not present with the other very long
chain fatty acid syndromes. A helpful memory aid for Zellweger syndrome is to think of Renee Zellweger, the actress, as a peroxide blonde - Zellweger is due to a
peroxisomal defect. Alternatively, imagine her hanging on a very long chain with a football referee (Refsum and Zellweger are diseases due to accumulation of very
long chain fatty acids).
QCCP2, Zellweger syndrome, Gaucher disease.

Front 21

What is the enzyme deficient in Gaucher disease?
A. galactose-1-phosphate uridyl transferase
B. gacheridase
C. glycosphingolipid
D. hexosaminidase A
E. glucocerebrosidase

Back 21

E. glucocerebrosidase.
The gene encoding the enzyme, glucocerebrosidase GBA is located on chromosome 1q. Both Gaucher and glucocerebrosidase have a G and U at the beginning of the
word.
QCCP2, Gaucher disease.