2013

NUTRITIONAL

DISORDERS

REVIEW -Part 2
and

PRIMARY

IMMUNODEFICIENCY
DISORDERS REVIEW
Barbara D. Bosch, M.D.

2013 Nutritional Disorders Review Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D

page 2

References for USMLE Step 1-format questions (with modifications):

Catalano E. Appleton & Lanqe Review of General Pathology. 4th ed. McGraw Hill Medical, 2003.
Fenderson BA, Strayer DS, Rubin R, Rubin E. Illustrated Q&A Review of Rubin's Pathology, 2nd
ed. Lippincott Williams & Wilkins, 201 1.

Goldberg J. Lanqe Practice Tests USMLE Step 1, 2nd ed. McGraw Hill Medical, 2006.
Kettering JD, Fletcher HM. PreTest Microbiology,

12th ed.

McGraw Hill Medical, 2007.

King MW. Lanae Q&A USMLE Step 1. 6,h ed. McGraw Hill Medical, 2008.
Klatt EC, Kumar V. Robbins and Cotran Review of Pathology, 3rd ed. Saunders Elsevier, 2010.
Klein RM, Enders GC. PreTest Anatomy, Histology & Cell Biology. 3rd ed. McGraw Hill Medical,

2007.

Le T, Klein J, Shivaram A. First Aid Q&A for the USMLE Step 1. McGraw Hill Medical, 2007.
Le T, Krause K, Klein J, Shivaram A. First Aid Cases for the USMLE Step 1. McGraw Hill Medical,

2006.
Mufson M. PreTest Pathophysiology, 3rd ed. McGraw Hill Medical, 2005.

PreTest Clinical Vignettes for the USMLE Step 1, 4th ed. McGraw Hill Medical, 2008.
Wilson GN. PreTest Biochemistry and Genetics. 3rd ed. McGraw Hill Medical, 2007.

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 3

A 37 year-old woman with a 20-year history of Crohn disease (a chronic inflammatory bowel

disease which frequently affects the terminal ileum) presents to her primary care physician

complaining of fatigue. Physical examination reveals tachycardia, pale conjunctivae, and a

sore, smooth, red tongue. Relevant laboratory findings include a hematocrit of 21% (normal 3646%), with a mean corpuscular volume of 105 fL (normal 80-100 fL). A slide of her peripheral

blood smear is provided below. Deficiency of which of the following vitamins is most likely?

A. ascorbic acid
B. calcitriol
C. cobalamin

D. folic acid

E. niacin
F. pyridoxine

'

G. retinol

H. thiamine

I. vitamin K

&

So .
o

If this patient's vitamin deficiency is not corrected, which of the following neurological signs /
symptoms would be most likely to develop?

A. confabulation and anterograde amnesia

B. horizontal gaze palsy and nystagmus
C. paresthesias and gait instability

D. proximal extremity and facial muscle weakness

E. upper extremity resting tremor and rigidity

2013 Nutritional Disorders Review Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D

What pathologic feature below is associated with the neurological findings of vitamin

page 4

B12

deficiency?

A. cerebellar atrophy
B. demyelination of the posterolateral columns of the spinal cord
C. hemorrhage in the mammillary bodies

D. neuronal degeneration of the basal ganglia

E. spinal cord compression

Which of the following laboratory results would support a diagnosis of cobalamin (vitamin B12)

deficiency?

A. decreased level of lactate dehydrogenase

B. elevated level of methylmalonic acid

C. elevated WBC count

D. hypochromic microcytic anemia

E. prolonged prothrombin time

Another frequent cause of vitamin

Bi2 deficiency is autoimmune chronic atrophic gastritis, which

results in mucosal destruction of the fundus and body of the stomach. What is the function of

the protein that is diminished in this disease process?

A. binding free vitamin
B.
C.

D.

E.

Bi2 in ileal cells for transport through the bloodstream

binding free vitamin Bi2 in the small intestine and then to ileal receptors
binding free vitamin Bi2 in the stomach
splitting R-protein / vitamin Bi2 complexes in the duodenum
splitting vitamin B12 from its exogenous ingested protein-bound form

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 5

Vitamin B12 - Cobalamin (water-soluble vitamin)

sources
meats, eggs and dairy products

(exclusively synthesized by
microorganisms)

vitamin Bi2 cleaved from its exogenous protein-bound form by pepsin

and complexed with salivary R-binders (stomach) complexes
absorption and transport

lysed by pancreatic proteases and vitamin B12 bound to intrinsic

factor (duodenum) IF receptor-mediated absorption (distal ileum)

=t>

vitamin

B12 bound to transcobalamin II (plasma) o uptake by

cells of the body

liver (amounts can last for several years)

storage

Dial

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 6

methylcobalamin - cofactor for methionine synthase (necessary to

convert homocysteine into methionine) and, in the process,

loses its methyl group which is donated by methyltetrahydrofolic

major biologic functions

acid to form tetrahydrofolic acid (active form of folate)

adenosylcobalamin - cofactor for methylmalonyl-CoA mutase

* I'd absorption (e.g., i'd gastric or pancreatic exocrine function; i'd

production of intrinsic factor, such as with autoimmune chronic

atrophic gastritis [pernicious anemia]; ileal resection or disease)
causes of deficiency

i'd intake (rare)

competition for dietary vitamin B12 (e.g., fish tapeworm infestation)

t'd requirement (e.g., pregnancy)

vitamin

B12 deficiency => "trapping" of folate in its methylated form <=>

impairment of thymidine, and ultimately DNA, synthesis

pathogenesis of

=>

defective

nuclear maturation and delayed cell division in rapidly proliferating

megaloblastic changes

cell types (e.g., erythrocytes)

megaloblastic anemia and megaloblastic changes (epithelium)

CNS myelin degeneration, especially in the posterolateral columns

of the spinal cord (subacute combined degeneration) =>

features of deficiency

paresthesias, loss of vibratory / position sensation, and

weakness, especially of the distal extremities

dUMP

N5' 10-Methylene FH4 X dTMP

Thymidylate
Synthetase

Homocysteine

Methionine Synthase

Methionine

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D page 7

Bonus questions:

A 40 year-old, chronically ill man from a Vietnamese village presents with painful sores around
his mouth. Physical examination reveals prominent fissures at the angles of his mouth.

Cheilosis in this patient is most likely caused by a deficiency of which of the following vitamins?
A. vitamin A
B. vitamin B,
C. vitamin

B2
D. vitamin Bt2

E. vitamin C
F. vitamin E
A j>5j/ear-old woman presents to your office complaining of intermittent skin flushing associated
well as heartburn for the last few months. Megadosing of which of the following
witpruritusas
vitamins may result in
symptoms?

these

A. cobalamin

B. niacin
C. riboflavin
D. vitamin A
E. vitamin C

F. vitamin D

A 15 month-old baby girl is brought to the emergency room by her parents for a 1-week history
of malaise, poor feeding, mild fever, and diarrhea. Physical examination is unremarkable. This

is the sixth such occasion for which the parents have brought their daughter to a physician.
Past visits have revealed repeated infections with Candida, cytomegalovirus and

Mycobacterium avium-intracellulare. A complete blood count (CBC) is remarkable only for a low
total lymphocyte count. Immunoglobulin levels are normal. A lymph node biopsy is remarkable
for paracortical cell depletion, but is otherwise normal. Which of the following is the most likely

diagnosis?

A. Bruton agammaglobulinemia
B. chronic granulomatous disease

C. severe combined immunodeficiency disease

D. thymic hypoplasia
E. Wiskott-Aldrich syndrome

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review: Barbara D. Bosch, M.D. page 8

A newborn girl is born with a small mouth, rather widely spaced eyes and low-set ears. Genetic
analysis shows a microdeletion on chromosome 22q1 1.2 leading to a diagnosis of an anomaly

which results from failure of the normal development of the third and fourth branchial pouches

during embryonic development. Which of the following could also be expected in a child with
this anomaly?

A. absence of serum immunoglobulins

B. excess activity of osteoclasts

C. increased numbers of cells in the deep cortex of the lymph nodes

D. increased serum Ca2+ levels

E. tetany

A neonate who is born with a cleft palate and abnormal facies becomes cyanotic and hypoxic

soon after birth. On physical examination, the neonatologist hears a crescendo-decrescendo

murmur with a harsh systolic ejection. Further investigation shows tetralogy of Fallot.

Laboratory tests reveal that the patient is hypocalcemic. This infant most likely has which of the

following conditions?
A. Bruton agammaglobulinemia

B. chronic granulomatous disease

C. DiGeorge syndrome

D. severe combined immunodeficiency

E. Wiskott-Aldrich syndrome

If you were to look at this newborn's spleen, which of the following regions would likely be
sparsely cellular?
A. capsule

B. red pulp cords

C. red pulp sinuses

D. white pulp follicles

E. white pulp periarteriolar lymphoid sheaths

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 9

DiGeorge syndrome Ithymic hypoplasia (partial or complete)

selective deficiency of T cells and T cell-mediated immunity

due to defective development of the 3rd and 4th pharyngeal pouches (give rise to the

thymus, parathyroid glands, parafollicular [C] cells of the thyroid, aortic arch, and
parts of the lips and ears)

majority due to chromosome 22q1 1 deletion

hypoplastic or absent thymus =t> defective T-cell maturation (low-normal lymphocyte
count, paracortical areas of lymph nodes and periarteriolar lymphoid sheaths of

spleen depleted) <=> I'd cell-mediated immunity => recurrent viral, fungal and
mycobacterial infections

absent or rudimentary parathyroid glands => hypocalcemia =0 tetany (often in first few

days of life)

congenital defects of the heart and great vessels, as well as facial abnormalities

occasionally treated with transplantation of fetal thymus or thymic epithelium (often not
needed)

Splenic Histology

white pulp

Spleen

H&E

"
splenic sinuses

white pulp

>
Jo

**

-V*

:f,r:

'j,

- .r

splenic
cord

macrophage

endothc

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch. M.D. page 10

A 12 year-old girl is brought to the pediatrician by her mother because of a fever. The physician
notes that the girl has features of albinism, and the mother states that her daughter has always

looked the way she does. The physician diagnoses the girl with a staphylococcal infection and
prescribes a course of antibiotics. Three months later, the child returns to the pediatrician with a
streptococcal infection. The patient's medical records indicate that she has had repeated bouts
of staphylococcal and streptococcal infections for her entire life. Photomicrographs of her

peripheral blood smear (left) and bone marrow aspirate (right) are included below.

A
,&s\

St

This patient most likely has which of the following types of immune deficiency?

A. Chediak-Higashi syndrome
B. chronic granulomatous disease
C. hyper-IgM syndrome

D. Job syndrome
E. selective IgA deficiency
F. severe combined immunodeficiency

G. Wiskott-Aldrich syndrome

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 11

Chediak-Higashi syndrome

rare, autosomal recessive disease characterized by a defective membrane-associated,

lysosomal trafficking regulator protein => abnormal organellar synthesis, trafficking

&/or fusion

generalized t'd fusion of cytoplasmic granules in leukocytes (especially neutrophils),

NK cells, melanocytes, platelets, and cells of the nervous system

enlarged lysosomes => neutropenia and impaired neutrophil function (e.g., chemotaxis,

phagocytosis, phagolysosome fusion, microbial killing)

recurrent infections,

especially by pyogenic bacteria

partial oculocutaneous albinism (due to melanin trapping in giant melanosomes)

mild bleeding tendency (abnormal dense bodies in platelets)

progressive neurologic dysfunction and eventual accelerated phase with

lymphoproliferative infiltrates

A 7 month-old male infant is admitted to the hospital with chronic diarrhea and an overall failure
to thrive. Review of his medical records reveals that he has had several episodes of bacterial

pneumonia and otitis media, along with oral candidiasis and herpes simplex virus
gingivostomatitis. Chest X-ray reveals the absence of a thymic shadow, and both B and T
lymphocytes are decreased in number in the peripheral blood. Serum calcium levels are within

normal limits. Which one of the following listed defects is associated with the X-linked recessive

form of this infant's immunodeficiency disease?

A. decreased production of NADPH oxidase
B. decreased synthesis of adenosine deaminase in lymphocytes
C. defects in the common gamma chain subunit of interleukin receptors

D. mutation in the gene coding for CD40L

E. mutation in the gene coding for the Wiskott-Aldrich syndrome protein (WASp)

Which of the following is the best therapy for the infant described above?

A. bone marrow transplant

B. IgG from pooled random donors
C. immunization with attenuated vaccines

D. infusion of the deficient enzyme

E. thymic grafting

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 12

Severe combined immunodeficiency diseases (SCID) - heterogeneous group

profound deficiency of BOTH cell-mediated and humoral immunity (although T-cell

immunity is usually more severely affected) due to abnormal development &/or

activation of both T and B lymphocytes

X-linked recessive form is the most common (50-60% of cases) due to an abnormal

gamma chain shared by several interleukin receptors

autosomal recessive forms are due to other abnormal receptor or signaling proteins,
impaired expression of class II MHC molecules (bare lymphocyte syndrome), or

PNP or * adenosine deaminase (ADA) deficiencies (which result in the accumulation

of metabolites toxic to developing T cells)

typical findings include virtual absence of systemic lymphoid tissue, severe lymphopenia

and scant immunoglobulins

if untreated, patients generally die by 1 year of age due to multiple, severe, recurrent
infections with all types of pathogens (bacterial, fungal, viral, protozoan)

individuals are also extremely susceptible to graft-versus-host disease

treated with early allogeneic stem cell transplantation

Which one of the following complement component deficiencies is associated with frequent

pyogenic bacterial infections?

A. C1q
B. C1 inhibitor

C. C2

D. C3
E. C4
Patients with C5-9 (membrane attack complex) complement deficiencies are most susceptible
to infections with which of the following pathogens?

A. Aspergillus sp.
B. Giardia lamblia
C. Neisseria sp.
D. Staphylococcus aureus
E, Streptococcus sp.

Genetic deficiencies of the complement system - rare disorders

C1(q, r or s), * C2 and C4 deficiencies autoimmune &/or immune complex diseases

(e.g., lupus-like disorder, glomerulonephritis)

C3 deficiency

frequent, serious, pyogenic bacterial infections

C5-9 deficiencies

recurrent disseminated infections by Neisseria

A 2 year-old girl is brought to the pediatrician for a routine

visit. History reveals recurrent infections and more falls
than usual lately. (Physical findings seen in this condition
are shown in the accompanying images.)

Suspecting an immune dysfunction, further testing is

performed. A defect in which of the following would be

most likely in this patient?
A. adenosine deaminase
B. CD40 ligand on CD4+ T-helper cells

C. DNA repair enzyme

D. interferon-y
E. LFA-1 adhesion proteins on phagocytes
F. tyrosine kinase

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M D. page 14

Ataxia-telangiectasia

autosomal recessive, multisystem disorder (due to ATM gene mutations and resultant
chromosomal instability)

ATM protein plays an important role in the recognition of damaged DNA and the
coordination of its repair, in addition to functions related to cell proliferation and
normal development / activity of the nervous and immune systems

characterized by progressive neurologic dysfunction, cerebellar ataxia, oculocutaneous

telangiectasia, abnormal sensitivity to radiation, impaired organ development,

variable types of immunodeficiency, and an T'd frequency of malignancies

A 2 year-old boy has had almost continuous infections since he was 6 months old. These
infections have included otitis media, pneumonia and impetigo. Organisms cultured have been
Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. He has also

had diarrhea, with Giardia lamblia cysts identified in stool specimens. The family history

indicates that an older brother with a similar condition died because of overwhelming infections.
The boy's five sisters and both parents are normal. Which of the following laboratory findings
would most likely be seen in this boy?

A. < 200 CD4+ T lymphocytes/pL

B. defective neutrophil NADPH oxidase function

C. deficiency of the late complement components (C5-9)

D. failure of phagosome-lysosome fusion within macrophages
E. markedly decreased immunoglobulin levels

Which of the following is important in the pathogenesis of this disease?

A. defect in a DNA repair enzyme

B. defective tyrosine kinase gene ( BTK gene)

C. deficiency of neutrophilic myeloperoxidase

D. failure of development of the third and fourth branchial pouches

E. failure of interferon-y production

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review: Barbara D. Bosch. M.D. page 15

Bruton (X-linked) agammaglobulinemia

selective deficiency of B cells, plasma cells and humoral immunity

defect due to a block in the maturation of pre-B cells to B cells - defective tyrosine

kinase (BTK) gene

eCNE MAPROW
Ptinpoum kloncal

I'd or absent B cells in blood and lymphoid

tissues (e.g., germinal centers), lack of
M,k*l cafe

I v-rct'Oil

plasma cells, and virtual absence of serum

ADA daftcloocy

immunoglobulins

severe recurrent infections beginning at 6-12

JX

inked SCIO

(Oto-ucrch-n*

months of age (when maternal

l-.ll.il! !..

-II

immunoglobulins become depleted)

susceptible to infections with pyogenic bacteria,

certain viruses (e.g., enteroviruses),

Giardia lamblia

treated with periodic gamma globulin infusions

patients also have an increased frequency of

autoimmune diseases

'I

''

mmmm

A 4 year-old boy presents to the physician with recurrent pyogenic infections. Physical
examination shows that the boy also has a pruritic papulovesicular dermatitis, as well as
scattered petechiae. Blood is drawn and sent for laboratory evaluation of platelets and

immunoglobulin levels. The results show a markedly low platelet count, a low serum IgM level,
and an elevated IgA level. This patient most likely has which of the following conditions?

A. ataxia-telangiectasia
B. Bruton agammaglobulinemia

C. Chediak-Higashi disease

D. chronic granulomatous disease

E. common variable immunodeficiency disease
F. thymic aplasia (DiGeorge syndrome)

G. Wiskott-Aldrich syndrome

MIC Clow

(tehaorcy

Ujluro

Icolli

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 16

Wiskott-Aldrich syndrome

diagnostic triad - immunodeficiency (cellular and humoral), thrombocytopenia (small

platelets) and eczema

X-linked recessive genetic defect in Wiskott-Aldrich syndrome protein (WASp) which

appears to function in cytoskeletal actin polymerization

early in the disease, lymphocyte count and thymus are normal, but poor antibody

response to polysaccharide antigens (especially susceptible to infections with

encapsulated pyogenic bacteria)

with t'ing age, progressive depletion of lymphocytes in the blood and T-cell
(paracortical) areas of lymph nodes

=>

variable loss of cellular immunity

commonly I'd IgM, normal IgG, T'd IgA and IgE

characterized by recurrent infections, bleeding complications and malignancies

(especially lymphomas)

can be treated with stem cell transplantation

Parents of an 18 month-old boy bring their child to a pediatrician as they are concerned about
their son's recurring skin and lung infections. Biopsy of one of the boy's current skin lesions
reveals aggregates of neutrophils surrounded by a rim of large, eosinophilic, epithelioid

macrophages (depicted in the image below). Culture of the lesion is positive for Staphylococcus

aureus. Which of the following would best account for this patient's condition?
A. absence of T-helper cell activity

B. adenosine deaminase enzyme deficiency

C. complement C3b opsonization abnormality

D. decreased hydrogen peroxide production

E. defective macrophage phagocytosis
What is the name of this disease?

Which of the following neutrophil functions is severely

impaired in this disorder?

A. adhesion to endothelial cells

B. chemotaxis
C. phagocytosis of bacteria

D. phagosome-lysosome fusion
E. microbial killing

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 17

Name the enzyme that is deficient in this disorder.

Why are streptococcal infections not usually found in patients with this disorder?

Chronic granulomatous disease (CGD)

rare disorder of neutrophils characterized by a lack of "respiratory burst" with

phagocytosis

defective activation of membrane NADPH-oxidase impaired production of superoxide

deficient H202 production in the phagolysosome o

failure of H202-MP0-halide killing system (converts H202 to HOCI [powerful oxidant])
anion during phagocytosis

-2/3 are X-linked recessive (neutrophils deficient in neutrophil cytochrome b); rest are
autosomal recessive (other components of NADPH-oxidase system affected)

frequent, severe, chronic bacterial infections with granulomatous abscesses of multiple

organs (including the subcutaneous tissue, lymph nodes, lungs, liver)

infectious pathogens are typically catalase-positive bacteria (e.g., Staphylococcus

aureus, Serratia, Salmonella , Escherichia coli) and fungi

treatment includes y-interferon

An 18 year-old woman presents to your clinic with a recurrent sinus infection. She has also
suffered from bronchitis, otitis media complicated by meningitis, diarrhea, and pneumonia over

the last year. You order serum studies, which demonstrate a markedly depressed IgG level and
subnormal serum IgA and IgM levels. You treat the sinusitis with antibiotics and suggest IV
gamma globulin therapy for treatment of her underlying condition. Which of the following would
most likely also be found in this patient?

A. absence of lymphoid germinal centers

B. failure of phagosome-lysosome fusion within macrophages
C. lymphadenopathy
D. lymphocytopenia
E. negative nitroblue tetrazolium dye reduction test

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch, M.D. page 18

Common variable immunodeficiency disease (CVID) - relatively common, heterogeneous

characterized by hypogammaglobulinemia (usually all immunoglobulins, occasionally

Sc-Vo.

only IgG)

often diagnosed irK{eenagers and young adults) congenital or acquired

usually due to an intrinsic B-cell defect (B cells can proliferate

in response to antigens, but fail to differentiate into plasma

cells); occasionally also T-cell dysfunction

__

typically a normal number of circulating B cells with markedly

~ce" areas (lymphoid follicles) in lymph nodes,

spleen and Gl tract (due to persistent antigen stimulation),

but no plasma cells; non-necrotizing granulomas may also

be seen

recurrent infections by pyogenic bacteria, as well as intestinal

COMMON VARIABLE IMMUNODEFICIENCY

DUODENAL NODULAR LYMPHOID
HYPERPLASIA (ENDOSCOPY)

infections with Giardia lambliaCX=*\ \

treated with periodic immunoglobulin infusions

associated with an T'd frequency of autoimmune diseases and lymphoma

S>

exrakoe

V.o&mu?\KVifceL.

Bonus questions:

What is the most common primary immunodeficiency in the U.S.?

A 22 year-old man is evaluated for repeated episodes of pulmonary infections, including a
recent one productive of foul, purulent sputum and accompanied by shortness of breath. Past

medical history is also significant for chronic sinus infections with mucopurulent discharge.
Physical examination is remarkable for scattered rhonchi and rales throughout all lung fields.

Imaging studies show abnormally dilated and thickened airways extending close to the pleural
surface and a cardiac silhouette in the right thorax. Bronchoscopy demonstrates numerous

mucopurulent plugs. Which of the following is most likely responsible for these findings?

A. abnormal neutrophilic function resulting in impaired degranulation

B. alpha-1 antiprotease deficiency (PiZZ phenotype)
C. cell membrane defect resulting in abnormally viscous glandular secretions

D. defect in ciliary motility due to the absence of dynein arms

E. hypersensitivity reaction associated with c-ANCA and granuloma formation

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review; Barbara D. Bosch. M.D. page 19

A 5 year-old boy has had multiple recurrent infections, including Pneumocystisjiroveci

pneumonia, Streptococcus pneumoniae otitis media and Pseudomonas aeruginosa urinary tract

infections. On physical examination, he is now noted to have pharyngeal erythema with an

exudate. Laboratory studies show hemoglobin 9.1 g/dL (nl 13.5-17.5); platelet count

130,900/mm3 (nl 150,000-400,000); and WBC count 3440/mm3 (nl 4500-11,000) with 47%
segmented neutrophils, 3% bands, 40% lymphocytes, and 10% monocytes. Serum
immunoglobulin levels are IgG 88 mg/dL (nl 650-1500); IgM 721 mg/dL (nl 40-345); and IgA
undetectable (nl 76-390 mg/dL). A peripheral blood smear shows nucleated RBCs. Which of
the following immunological defects is most likely in this patient?
A. a defect in DNA repair enzymes

B. a defect in LFA-1 adhesion proteins on phagocytes

C. abnormal CD40-CD40L interaction

D. absence of adenosine deaminase

E. deletion of chromosome 22q1 1

F. failure of interferon-y production
G. lack of IgA production by B lymphocytes
H. mutation in the BTK gene

Where does immunoglobulin switching from IgM to IgG primarily occur?

A. bone marrow
B. germinal centers

C. peripheral blood

D. splenic red pulp

E. thymus

A 24 year-old woman with a history of allergic rhinitis is involved in an automobile accident and

sustains a splenic laceration. She undergoes abdominal surgery and is then transfused with
four units of blood of the appropriate ABO and Rh type. As the transfusion progresses, she
becomes rapidly hypotensive and develops airway edema, consistent with anaphylaxis. Which

of the following pre-existing conditions best accounts for these symptoms?

A. C1 esterase inhibitor deficiency

B. common variable immunodeficiency

C. DiGeorge syndrome

D. hyper-IgM syndrome
E. selective IgA deficiency
F. Wiskott-Aldrich syndrome

2013 Nutritional Disorders Review - Part 2 and Primary Immunodeficiency Disorders Review: Barbara D. Bosch, M D. page 20

A 15 year-old boy is brought to the emergency department because of the acute onset of fever,

chills and a productive cough. Samples taken of the sputum show a-hemolytic gram-positive
diplococci that show a positive quellung reaction. The patient says that he has had similar

infections over the past year. A peripheral blood smear is done, and results show several

sickle-shaped RBCs. Which of the following explains why this patient is susceptible to this
particular type of infection?

A. bone marrow infiltration resulting in neutropenia and compromised immune function

B. large vessel occlusions in the cerebral vasculature resulting in neurologic events and

aspiration pneumonia
C. microvascular infarcts resulting in pulmonary failure

D. microvascular infarcts resulting in splenic dysfunction

E. vaso-occlusion in the renal medulla resulting in renal failure and uremia