A 40-day-old child presents to a physician for the first time for a well-child visit. The mother is a 22-year-old college student who opted for a home birth. Upon examination, the child weighs 4.0 kg (8.8 lbs) and has intact reflexes. The umbilical cord is still attached and looks erythematous and indurated. A complete blood cell count reveals leukocytosis. Immunoglobulin levels are normal. A flow cytometry analysis is performed. Which of the following markers will most likely be deficient in this child?
Q2
A 6-year-old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases?
Q3
A 24-year-old woman comes to the clinic complaining of headache and sinus drainage for the past 13 days. She reports cold-like symptoms 2 weeks ago that progressively got worse. The patient endorses subjective fever, congestion, sinus headache, cough, and chills. She claims that this is her 5th episode within the past year and is concerned if “there’s something else going on.” Her medical history is significant for asthma that is adequately controlled with her albuterol inhaler. Her laboratory findings are shown below:
Serum:
Hemoglobin: 16.2 g/dL
Hematocrit: 39 %
Leukocyte count: 7,890/mm^3 with normal differential
Platelet count: 200,000/mm^3
IgA: 54 mg/dL (Normal: 76-390 mg/dL)
IgE: 0 IU/mL (Normal: 0-380 IU/mL)
IgG: 470 mg/dL (Normal: 650-1500 mg/dL)
IgM: 29 mg/dL (Normal: 40-345 mg/dL)
What is the most likely diagnosis?
Q4
A pathologist performed an autopsy on an 18-month-old infant boy who died of pneumonia. Clinical notes revealed the infant had repeated respiratory infections that started after he was weaned off of breast-milk. Laboratory investigation revealed hypogammaglobulinemia and an absence of B-cells. T-cell levels were normal. Histological evaluation of an axillary lymph node revealed an absence of germinal centers. Which of the following is the mode of inheritance of the disorder that afflicted this infant?
Q5
A 2-year-old girl presents with high fever, restlessness, and a generalized papulovesicular rash. Past medical history is significant for varicella pneumonia and disseminated cytomegalovirus infection during the 1st year of her life. She was delivered vaginally to a primigravid 22-year-old woman from an uncomplicated pregnancy and was breastfed up to 9 months of age. She is up to date with her vaccines and is meeting all developmental milestones. The vital signs include blood pressure 70/45 mm Hg, heart rate 110/min, respiratory rate 27/min, and temperature 38.0°C (100.4°F). Physical examination demonstrates a generalized papulovesicular rash without a tendency to fuse. The rest of the physical examination is unremarkable for any pathological findings. Disseminated herpes virus infection is suspected. The child is also assessed for primary immunodeficiency. Flow cytometry reveals the absence of CD56 positive cells. Which of the following is true regarding these cells in this patient?
Q6
A 9-month-old girl is brought in by her father for a scheduled check-up with her pediatrician. He states that over the past 4-5 months she has had multiple ear infections. She was also hospitalized for an upper respiratory infection 2 months ago. Since then she has been well. She has started to pull herself up to walk. Additionally, the patient’s medical history is significant for eczema and allergic rhinitis. The father denies any family history of immunodeficiencies. There are no notable findings on physical exam. Labs are remarkable for low IgG levels with normal IgA, IgE, and IgM levels. Which of the following is the most likely etiology for the patient’s presentation?
Q7
A 6-month-old baby boy presents to his pediatrician for the evaluation of recurrent bacterial infections. He is currently well but has already been hospitalized multiple times due to his bacterial infections. His blood pressure is 103/67 mm Hg and heart rate is 74/min. Physical examination reveals light-colored skin and silver hair. On examination of a peripheral blood smear, large cytoplasmic vacuoles containing microbes are found within the neutrophils. What diagnosis do these findings suggest?
Q8
You are seeing an otherwise healthy 66-year-old male in clinic who is complaining of localized back pain and a new rash. On physical exam, his vital signs are within normal limits. You note a vesicular rash restricted to the upper left side of his back. In order to confirm your suspected diagnosis, you perform a diagnostic test. What would you expect to find on the diagnostic test that was performed?
Q9
A 1-year-old infant is brought to the emergency department by his parents because of fever and rapid breathing for the past 2 days. He had a mild seizure on the way to the emergency department and developed altered sensorium. His mother states that the patient has had recurrent respiratory infections since birth. He was delivered vaginally at term and without complications. He is up to date on his vaccines and has met all developmental milestones. His temperature is 37.0°C (98.6°F), pulse rate is 200/min, and respirations are 50/min. He is lethargic, irritable, and crying excessively. Physical examination is notable for a small head, an elongated face, broad nose, low set ears, and cleft palate. Cardiopulmonary exam is remarkable for a parasternal thrill, grade IV pansystolic murmur, and crackles over both lung bases. Laboratory studies show hypocalcemia and lymphopenia. Blood cultures are drawn and broad-spectrum antibiotics are started, and the child is admitted to the pediatric intensive care unit. The intensivist suspects a genetic abnormality and a fluorescence in situ hybridization (FISH) analysis is ordered which shows 22q11.2 deletion. Despite maximal therapy, the infant succumbs to his illness. The parents of the child request an autopsy. Which of the following findings is the most likely to be present on autopsy?
Q10
An 8-year-old boy is brought to the pediatrician because his mother is concerned about recent behavioral changes. His mother states that she has started to notice that he is slurring his speech and seems to be falling more than normal. On exam, the pediatrician observes the boy has pes cavus, hammer toes, and kyphoscoliosis. Based on these findings, the pediatrician is concerned the child has a trinucleotide repeat disease. Which of the following trinucleotide repeats is this child most likely to possess?
Immunodeficiency disorders US Medical PG Practice Questions and MCQs
Question 1: A 40-day-old child presents to a physician for the first time for a well-child visit. The mother is a 22-year-old college student who opted for a home birth. Upon examination, the child weighs 4.0 kg (8.8 lbs) and has intact reflexes. The umbilical cord is still attached and looks erythematous and indurated. A complete blood cell count reveals leukocytosis. Immunoglobulin levels are normal. A flow cytometry analysis is performed. Which of the following markers will most likely be deficient in this child?
A. CD1a
B. CD56
C. CD3
D. CD18 (Correct Answer)
E. CD21
Explanation: ***CD18***
- The child's presentation with an **erythematous and indurated umbilical cord** that is still attached, along with **leukocytosis**, is highly suggestive of **Leukocyte Adhesion Deficiency Type 1 (LAD-1)**.
- LAD-1 is caused by a defect in the **integrin beta-2 subunit (CD18)**, which is crucial for leukocyte adhesion and extravasation to sites of infection.
*CD1a*
- **CD1a** is a marker for **Langerhans cells** and immature dendritic cells, which are involved in antigen presentation.
- A deficiency in CD1a is not typically associated with the recurrent bacterial infections and impaired umbilical cord separation seen in this case.
*CD56*
- **CD56** is a marker for **natural killer (NK) cells**, which are important for viral immunity and tumor surveillance.
- While NK cell deficiencies can lead to recurrent infections, the clinical picture here, with delayed umbilical cord detachment and bacterial infection, points more specifically to a defect in neutrophil function.
*CD3*
- **CD3** is a marker for **T lymphocytes**, which are central to cell-mediated immunity.
- Deficiencies in CD3 or T cells typically lead to severe combined immunodeficiency (SCID) with opportunistic infections, which usually present earlier and with more widespread symptoms than described.
*CD21*
- **CD21** (also known as the C3d receptor or CR2) is primarily found on **B lymphocytes** and follicular dendritic cells.
- It plays a role in B cell activation and memory, but a deficiency would not explain the specific constellation of symptoms, particularly the umbilical cord infection and leukocytosis.
Question 2: A 6-year-old child presents for evaluation of a medical condition associated with recurrent infections. After reviewing all of the medical history, gene therapy is offered to treat a deficiency in adenosine deaminase (ADA). ADA deficiency is the most common autosomal recessive mutation in which of the following diseases?
A. Wiskott-Aldrich Syndrome
B. Bruton's Agammaglobulinemia
C. Severe Combined Immunodeficiency (Correct Answer)
D. DiGeorge Syndrome
E. Hyper-IgM Syndrome
Explanation: ***Severe Combined Immunodeficiency***
- **Adenosine deaminase (ADA) deficiency** leads to the accumulation of toxic metabolites that impair lymphocyte development and function, primarily affecting **T and B cells**, which is a common cause of SCID.
- Patients with SCID present with **recurrent, severe infections** due to profound immunodeficiency, making them candidates for treatments like gene therapy.
*Wiskott-Aldrich Syndrome*
- This is an **X-linked recessive disorder** characterized by eczema, thrombocytopenia, and immunodeficiency, but it is caused by a mutation in the **WASP gene**, not ADA deficiency.
- While it involves immunodeficiency and recurrent infections, the underlying genetic defect and specific clinical triad are distinct from ADA deficiency.
*Bruton's Agammaglobulinemia*
- This is an **X-linked recessive disorder** caused by a defect in the **BTK gene**, leading to a lack of mature B cells and hence very low levels of immunoglobulins.
- While it results in recurrent bacterial infections due to absent antibodies, its genetic cause and primary immunological defect (B cell specific) differ from ADA deficiency.
*DiGeorge Syndrome*
- This is a developmental disorder caused by a **microdeletion on chromosome 22q11.2**, leading to abnormal development of the third and fourth pharyngeal pouches.
- It results in **T-cell deficiency** due to thymic aplasia/hypoplasia, hypocalcemia due to parathyroid hypoplasia, and congenital heart defects, but not ADA deficiency.
*Hyper-IgM Syndrome*
- This syndrome is characterized by normal or elevated IgM levels and deficiencies in other immunoglobulins (IgG, IgA, IgE), largely due to defects in **CD40-CD40L interaction** or other genes involved in isotype switching.
- Patients suffer from recurrent infections and opportunistic infections but the genetic basis and specific immunological defect are distinct from ADA deficiency.
Question 3: A 24-year-old woman comes to the clinic complaining of headache and sinus drainage for the past 13 days. She reports cold-like symptoms 2 weeks ago that progressively got worse. The patient endorses subjective fever, congestion, sinus headache, cough, and chills. She claims that this is her 5th episode within the past year and is concerned if “there’s something else going on.” Her medical history is significant for asthma that is adequately controlled with her albuterol inhaler. Her laboratory findings are shown below:
Serum:
Hemoglobin: 16.2 g/dL
Hematocrit: 39 %
Leukocyte count: 7,890/mm^3 with normal differential
Platelet count: 200,000/mm^3
IgA: 54 mg/dL (Normal: 76-390 mg/dL)
IgE: 0 IU/mL (Normal: 0-380 IU/mL)
IgG: 470 mg/dL (Normal: 650-1500 mg/dL)
IgM: 29 mg/dL (Normal: 40-345 mg/dL)
What is the most likely diagnosis?
A. Wiskott-Aldrich syndrome
B. Selective IgA deficiency
C. Common variable immunodeficiency (Correct Answer)
D. Ataxia-telangiectasia
E. X-linked agammaglobinemia
Explanation: ***Common variable immunodeficiency***
- This patient presents with recurrent sinopulmonary infections (5 episodes in the past year) and significantly **low levels of IgA, IgG, and IgM**, which is characteristic of **common variable immunodeficiency (CVID)**.
- CVID often manifests in adulthood (patient is 24) with infections, and laboratory findings typically show **decreased levels of at least two immunoglobulin classes**, most commonly IgG and IgA, with or without low IgM.
*Wiskott-Aldrich syndrome*
- This syndrome is characterized by the triad of **thrombocytopenia**, **eczema**, and **recurrent infections**, often presenting in early childhood.
- While recurrent infections are present, this patient does not have thrombocytopenia or eczema, and the immunoglobulin profile for Wiskott-Aldrich Syndrome typically shows **low IgM** with **normal to elevated IgA and IgE**.
*Selective IgA deficiency*
- This condition is defined by **isolated low IgA levels** (<7 mg/dL), with normal levels of IgG and IgM.
- This patient has low IgA, but also significantly low IgG and IgM, ruling out a selective IgA deficiency.
*Ataxia-telangiectasia*
- This is a rare, autosomal recessive disorder characterized by **ataxia**, **telangiectasias**, and **immunodeficiency** (often involving IgA and IgE, but can also affect IgG subclasses).
- The patient does not present with ataxia or telangiectasias, which are hallmark features of this syndrome.
*X-linked agammaglobinemia*
- This condition is almost exclusively found in **males** and typically presents with recurrent infections in **infancy** after maternal antibodies wane.
- It is characterized by **profoundly low or absent levels of all immunoglobulin classes** (IgG, IgA, IgM) and the **absence of B cells**, which is not entirely consistent with this female patient's presentation and immunoglobulin levels.
Question 4: A pathologist performed an autopsy on an 18-month-old infant boy who died of pneumonia. Clinical notes revealed the infant had repeated respiratory infections that started after he was weaned off of breast-milk. Laboratory investigation revealed hypogammaglobulinemia and an absence of B-cells. T-cell levels were normal. Histological evaluation of an axillary lymph node revealed an absence of germinal centers. Which of the following is the mode of inheritance of the disorder that afflicted this infant?
A. Autosomal dominant
B. Mitochondrial inheritance
C. Autosomal recessive
D. X-linked recessive (Correct Answer)
E. X-linked dominant
Explanation: ***X-linked recessive***
- This presentation, including **recurrent respiratory infections** after weaning, **hypogammaglobulinemia**, absence of B-cells, normal T-cells, and absent germinal centers, is classic for **X-linked agammaglobulinemia (XLA)**, also known as Bruton's agammaglobulinemia.
- XLA is caused by a mutation in the **Bruton's tyrosine kinase (BTK)** gene on the X chromosome, leading to a block in B-cell maturation.
*Autosomal dominant*
- Autosomal dominant disorders typically affect males and females equally, and often a parent is also affected; this pattern is not consistent with the described **X-linked inheritance** characteristic of XLA.
- While some immune deficiencies can be autosomal dominant, the specific constellation of symptoms strongly points away from this mode of inheritance for this particular disease.
*Mitochondrial inheritance*
- Mitochondrial disorders are transmitted maternally, affecting all offspring of an affected mother, which is not characteristic of the described **immunodeficiency's inheritance pattern**.
- These disorders typically manifest with **neurological** or **muscular dysfunction**, which are not the primary symptoms here.
*Autosomal recessive*
- Autosomal recessive disorders affect individuals who inherit two copies of the mutated gene (one from each parent), and often there's a family history of affected siblings but not typically affected parents.
- While some combined immunodeficiencies can be autosomal recessive, the specific B-cell maturation defect described here for XLA is **X-linked recessive**.
*X-linked dominant*
- X-linked dominant disorders affect both males and females, with an affected father passing the trait to all his daughters but none of his sons, and an affected mother having a 50% chance of passing it to each child regardless of sex.
- This pattern of inheritance is **not consistent** with the manifestation and prevalence of XLA, which primarily affects males due to its recessive nature.
Question 5: A 2-year-old girl presents with high fever, restlessness, and a generalized papulovesicular rash. Past medical history is significant for varicella pneumonia and disseminated cytomegalovirus infection during the 1st year of her life. She was delivered vaginally to a primigravid 22-year-old woman from an uncomplicated pregnancy and was breastfed up to 9 months of age. She is up to date with her vaccines and is meeting all developmental milestones. The vital signs include blood pressure 70/45 mm Hg, heart rate 110/min, respiratory rate 27/min, and temperature 38.0°C (100.4°F). Physical examination demonstrates a generalized papulovesicular rash without a tendency to fuse. The rest of the physical examination is unremarkable for any pathological findings. Disseminated herpes virus infection is suspected. The child is also assessed for primary immunodeficiency. Flow cytometry reveals the absence of CD56 positive cells. Which of the following is true regarding these cells in this patient?
A. They differentiate from the myeloid progenitor
B. They have cell surface receptors for detecting MHC 1 on other cells (Correct Answer)
C. These cells also express the T cell receptor
D. They are the part of adaptive immunity
E. They need MHC class 1 to be expressed on the cell to eliminate it
Explanation: ***They have cell surface receptors for detecting MHC 1 on other cells***
- **CD56 positive cells**, or **Natural Killer (NK) cells**, are key components of the **innate immune system** that monitor other cells for the presence or absence of **MHC class I molecules**.
- **NK cells** express inhibitory receptors that bind to **MHC class I molecules** on healthy cells, preventing their lysis. When MHC class I is absent (as seen in some virally infected or cancerous cells), these inhibitory signals are lost, leading to **NK cell activation** and target cell killing.
*They differentiate from the myeloid progenitor*
- **CD56 positive cells (NK cells)** differentiate from a **common lymphoid progenitor**, not a myeloid progenitor.
- **Myeloid progenitors** give rise to granulocytes, monocytes, macrophages, and dendritic cells, among others, but not NK cells.
*These cells also express the T cell receptor*
- **CD56 positive cells (NK cells)** do **not express T cell receptors (TCRs)**; the absence of TCRs is a distinguishing feature that differentiates them from T lymphocytes.
- **NK cells** utilize a different set of activating and inhibitory receptors to recognize and kill target cells, independent of **MHC presentation**.
*They are the part of adaptive immunity*
- **CD56 positive cells (NK cells)** are a crucial part of the **innate immune system**, providing a rapid, non-specific response to infected or malignant cells.
- Unlike adaptive immune cells (T and B lymphocytes), they do not undergo **clonal expansion** or develop **immunological memory** in the classical sense.
*They need MHC class 1 to be expressed on the cell to eliminate it*
- **CD56 positive cells (NK cells)** are activated to kill cells that **LACK MHC class I expression**, a mechanism known as "missing-self" recognition.
- Cells with normal **MHC class I expression** are typically protected from **NK cell lysis** through inhibitory signals.
Question 6: A 9-month-old girl is brought in by her father for a scheduled check-up with her pediatrician. He states that over the past 4-5 months she has had multiple ear infections. She was also hospitalized for an upper respiratory infection 2 months ago. Since then she has been well. She has started to pull herself up to walk. Additionally, the patient’s medical history is significant for eczema and allergic rhinitis. The father denies any family history of immunodeficiencies. There are no notable findings on physical exam. Labs are remarkable for low IgG levels with normal IgA, IgE, and IgM levels. Which of the following is the most likely etiology for the patient’s presentation?
A. Failure of B-cell differentiation
B. Defect in Bruton tyrosine kinase
C. Delayed onset of normal immunoglobulins (Correct Answer)
D. Adenosine deaminase deficiency
E. Impaired T cell signaling
Explanation: ***Delayed onset of normal immunoglobulins***
- The patient's presentation with recurrent ear infections, a URI, and low **IgG** levels in the setting of normal **IgA, IgE, and IgM** is characteristic of **transient hypogammaglobulinemia of infancy (THI)**. This resolves spontaneously as the infant's immune system matures.
- THI is a condition where the **physiologic nadir** of IgG, typically occurring between 3-6 months, is more prolonged and pronounced than usual, leading to increased susceptibility to infections.
*Failure of B-cell differentiation*
- This would lead to a more profound impairment of immunoglobulin production, affecting multiple **immunoglobulin classes** (IgA, IgM, IgG) more severely than seen here.
- Conditions involving failure of B-cell differentiation, such as **Common Variable Immunodeficiency (CVID)**, typically present later in childhood or adulthood with recurrent severe infections and panhypogammaglobulinemia.
*Defect in Bruton tyrosine kinase*
- A defect in **Bruton tyrosine kinase (BTK)** is responsible for **X-linked agammaglobulinemia (XLA)**, characterized by an absence or severe deficiency of B cells, and thus **markedly decreased levels of all immunoglobulins** (IgG, IgA, IgM).
- The patient here has normal IgA and IgM, and only low IgG, which is not consistent with XLA.
*Adenosine deaminase deficiency*
- This deficiency causes **severe combined immunodeficiency (SCID)**, affecting both **T-cell and B-cell function**, leading to profoundly low levels of all immunoglobulins and severe, life-threatening infections from early infancy.
- The patient's relatively mild course with only recurrent ear infections and a good developmental milestone (pulling to walk) does not fit the SCID picture.
*Impaired T cell signaling*
- Impaired T cell signaling would result in defects in **cell-mediated immunity** and typically affect **humoral immunity** as well due to the need for T cell help in antibody production.
- This would usually lead to low levels of multiple immunoglobulin classes and a broad susceptibility to various pathogens, including **opportunistic infections**, which is not indicated in this case.
Question 7: A 6-month-old baby boy presents to his pediatrician for the evaluation of recurrent bacterial infections. He is currently well but has already been hospitalized multiple times due to his bacterial infections. His blood pressure is 103/67 mm Hg and heart rate is 74/min. Physical examination reveals light-colored skin and silver hair. On examination of a peripheral blood smear, large cytoplasmic vacuoles containing microbes are found within the neutrophils. What diagnosis do these findings suggest?
A. Leukocyte adhesion deficiency-1
B. Common variable immunodeficiency
C. Acquired immunodeficiency syndrome
D. Chediak-Higashi syndrome (Correct Answer)
E. Congenital thymic aplasia
Explanation: **Chediak-Higashi syndrome**
- The presence of **recurrent bacterial infections**, **light-colored skin and silver hair**, and **large cytoplasmic vacuoles within neutrophils** is pathognomonic for Chediak-Higashi syndrome.
- This condition is an **autosomal recessive disorder** characterized by impaired lysosomal trafficking, affecting phagocyte function and melanosome formation.
*Leukocyte adhesion deficiency-1*
- This disorder is characterized by **recurrent bacterial infections** due to a defect in integrins, preventing neutrophils from adhering to endothelial cells and migrating to infection sites.
- However, it typically presents with **delayed umbilical cord separation** and lacks the distinctive features of light-colored skin/silver hair and giant cytoplasmic granules.
*Common variable immunodeficiency*
- This condition is characterized by **recurrent bacterial infections** due to low levels of immunoglobulins, leading to impaired B-cell function.
- It typically presents later in childhood or adulthood and does not involve abnormalities in skin pigmentation or neutrophil morphology.
*Acquired immunodeficiency syndrome*
- **AIDS** is caused by the **Human Immunodeficiency Virus (HIV)** and leads to a progressive decline in CD4+ T cells, resulting in opportunistic infections.
- While it causes recurrent infections, the clinical presentation in a **6-month-old infant** with silver hair and giant neutrophil granules is not consistent with AIDS unless there's a strong perinatal exposure history, which is not mentioned.
*Congenital thymic aplasia*
- Also known as **DiGeorge syndrome**, this condition involves **T-cell immunodeficiency** due to hypoplasia or aplasia of the thymus, leading to recurrent viral, fungal, and parasitic infections.
- It is also associated with **hypocalcemia** and **congenital heart defects**, but it does not present with recurrent bacterial infections combined with light skin/silver hair and giant neutrophil granules.
Question 8: You are seeing an otherwise healthy 66-year-old male in clinic who is complaining of localized back pain and a new rash. On physical exam, his vital signs are within normal limits. You note a vesicular rash restricted to the upper left side of his back. In order to confirm your suspected diagnosis, you perform a diagnostic test. What would you expect to find on the diagnostic test that was performed?
A. Gram negative bacilli
B. Branching pseudohyphae
C. Pear shaped motile cells
D. Multinucleated giant cells (Correct Answer)
E. Gram positive cocci
Explanation: ***Multinucleated giant cells***
- The patient's presentation of a **unilateral, vesicular rash** in an older adult, along with localized back pain, is highly suggestive of **herpes zoster (shingles)**.
- A Tzanck smear, a common diagnostic test for vesicular lesions, would reveal **multinucleated giant cells** and **intranuclear inclusions**, characteristic cytopathic effects of herpesviruses like VZV.
*Gram negative bacilli*
- This finding would suggest a **bacterial infection**, typically not associated with vesicular rashes like shingles.
- Gram-negative bacilli are often implicated in conditions such as **urinary tract infections** or **sepsis**, not dermatological viral infections.
*Branching pseudohyphae*
- This microscopic feature is characteristic of **fungal infections**, specifically **Candida species**, which present as a candidiasis rash, not a dermatomal vesicular rash.
- Fungal rashes are typically erythematous and can be pruritic but do not usually form discrete vesicles in a dermatomal distribution.
*Pear shaped motile cells*
- This describes **Trichomonas vaginalis**, a parasite causing sexually transmitted infections, primarily **vaginitis** or **urethritis**.
- This finding would be completely unrelated to a vesicular skin rash or the suspected diagnosis of shingles.
*Gram positive cocci*
- This finding is indicative of a **bacterial infection**, such as those caused by **Staphylococcus aureus** or **Streptococcus pyogenes**.
- While these bacteria can cause skin infections (e.g., impetigo, cellulitis), they do not produce the classic unilateral vesicular rash of shingles and would not involve multinucleated giant cells on microscopy.
Question 9: A 1-year-old infant is brought to the emergency department by his parents because of fever and rapid breathing for the past 2 days. He had a mild seizure on the way to the emergency department and developed altered sensorium. His mother states that the patient has had recurrent respiratory infections since birth. He was delivered vaginally at term and without complications. He is up to date on his vaccines and has met all developmental milestones. His temperature is 37.0°C (98.6°F), pulse rate is 200/min, and respirations are 50/min. He is lethargic, irritable, and crying excessively. Physical examination is notable for a small head, an elongated face, broad nose, low set ears, and cleft palate. Cardiopulmonary exam is remarkable for a parasternal thrill, grade IV pansystolic murmur, and crackles over both lung bases. Laboratory studies show hypocalcemia and lymphopenia. Blood cultures are drawn and broad-spectrum antibiotics are started, and the child is admitted to the pediatric intensive care unit. The intensivist suspects a genetic abnormality and a fluorescence in situ hybridization (FISH) analysis is ordered which shows 22q11.2 deletion. Despite maximal therapy, the infant succumbs to his illness. The parents of the child request an autopsy. Which of the following findings is the most likely to be present on autopsy?
A. Aplastic thymus (Correct Answer)
B. Hypercellular bone marrow
C. Accessory spleen
D. Hypertrophy of Hassall's corpuscles
E. Absent follicles in the lymph nodes
Explanation: ***Aplastic thymus***
- This infant's presentation with 22q11.2 deletion, recurrent respiratory infections, hypocalcemia, and congenital heart disease (parasternal thrill, pansystolic murmur) is classic for **DiGeorge syndrome**.
- **DiGeorge syndrome** is characterized by thymic aplasia or hypoplasia, leading to **T-cell immunodeficiency**, and parathyroid hypoplasia, resulting in **hypocalcemia**.
*Hypercellular bone marrow*
- **Hypercellular bone marrow** indicates increased hematopoietic activity and is not a characteristic finding in DiGeorge syndrome.
- In immunodeficiency states like DiGeorge, the bone marrow itself is often normal or may show lymphoid depletion.
*Accessory spleen*
- **Accessory spleen** is a common congenital anomaly and is not specifically associated with DiGeorge syndrome or its immunodeficiency.
- While it can occur in individuals with DiGeorge syndrome, it is not a direct pathological consequence of the 22q11.2 deletion.
*Hypertrophy of Hassall's corpuscles*
- **Hassall's corpuscles** are found in the medulla of the thymus, and their hypertrophy would indicate an active or hyperplastic thymus, which is contrary to the **thymic aplasia/hypoplasia** seen in DiGeorge syndrome.
- In DiGeorge syndrome, the thymus is either absent or severely underdeveloped.
*Absent follicles in the lymph nodes*
- **Absent follicles in the lymph nodes** would indicate a B-cell deficiency, as follicles are primarily composed of B lymphocytes.
- DiGeorge syndrome primarily affects **T-cell development** due to thymic abnormalities, not B-cell development or lymph node follicular formation directly.
Question 10: An 8-year-old boy is brought to the pediatrician because his mother is concerned about recent behavioral changes. His mother states that she has started to notice that he is slurring his speech and seems to be falling more than normal. On exam, the pediatrician observes the boy has pes cavus, hammer toes, and kyphoscoliosis. Based on these findings, the pediatrician is concerned the child has a trinucleotide repeat disease. Which of the following trinucleotide repeats is this child most likely to possess?
A. CTG
B. GAA (Correct Answer)
C. CGG
D. CAG
E. GCC
Explanation: ***GAA***
- This trinucleotide repeat is associated with **Friedreich's ataxia**, an autosomal recessive neurodegenerative disorder.
- The presented symptoms of **ataxia** (slurred speech, falling), **pes cavus**, **hammer toes**, and **kyphoscoliosis** are classic features of Friedreich's ataxia.
*CTG*
- This trinucleotide repeat is associated with **myotonic dystrophy type 1**, an autosomal dominant disorder.
- While it causes muscle weakness, it is characterized by **myotonia** (delayed muscle relaxation), cataracts, and frontal baldness, which are not described here.
*CGG*
- This trinucleotide repeat is associated with **fragile X syndrome**, an X-linked dominant disorder.
- Fragile X syndrome primarily causes intellectual disability, behavioral issues (e.g., autism spectrum disorder), and characteristic facial features, but not the specific neurological and orthopedic findings seen in this patient.
*CAG*
- This trinucleotide repeat is associated with several neurodegenerative diseases, including **Huntington's disease**, spinocerebellar ataxias, and **dentatorubral-pallidoluysian atrophy**.
- Huntington's disease, for example, presents with chorea, cognitive decline, and psychiatric symptoms, differing from the patient's presentation.
*GCC*
- This trinucleotide repeat is associated with **fragile X-associated tremor/ataxia syndrome (FXTAS)**.
- FXTAS typically affects older adult carriers of premutation alleles for fragile X, presenting with intention tremor and gait ataxia, not the early childhood onset and specific orthopedic deformities seen here.
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