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Questions and Answers
What is the primary population affected by the acute neuronopathic form?
What is the primary population affected by the acute neuronopathic form?
Which of the following is NOT a cause of neutropenia?
Which of the following is NOT a cause of neutropenia?
What is the absolute count threshold that defines monocytosis?
What is the absolute count threshold that defines monocytosis?
Which condition is associated with lymphocytosis in adults?
Which condition is associated with lymphocytosis in adults?
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Among the following, which is a recognized infectious cause of lymphocytosis?
Among the following, which is a recognized infectious cause of lymphocytosis?
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What is the primary cause of problems in patients with Lazy Leukocyte Syndrome?
What is the primary cause of problems in patients with Lazy Leukocyte Syndrome?
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Which of the following is NOT a consequence of Leukocyte Adhesion Disorders (LADs)?
Which of the following is NOT a consequence of Leukocyte Adhesion Disorders (LADs)?
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In which type of LAD do patients exhibit a mutation in the ITGB2 gene?
In which type of LAD do patients exhibit a mutation in the ITGB2 gene?
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What is a clinical feature of Job’s Syndrome?
What is a clinical feature of Job’s Syndrome?
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What is a common finding in LAD II patients?
What is a common finding in LAD II patients?
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What specific mutation causes LAD III?
What specific mutation causes LAD III?
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Which clinical manifestation is indicative of CHS1 LYST gene mutation?
Which clinical manifestation is indicative of CHS1 LYST gene mutation?
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What is the main treatment for individuals with Leukocyte Adhesion Disorders?
What is the main treatment for individuals with Leukocyte Adhesion Disorders?
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Which condition is primarily associated with defects in neutrophil motility?
Which condition is primarily associated with defects in neutrophil motility?
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What is NOT a typical finding in patients with LAD I?
What is NOT a typical finding in patients with LAD I?
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What is the primary immune defect observed in WHIM syndrome?
What is the primary immune defect observed in WHIM syndrome?
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Which of the following is a symptom of Chronic Granulomatous Disease (CGD)?
Which of the following is a symptom of Chronic Granulomatous Disease (CGD)?
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What results in the neutrophil accumulation in the bone marrow in WHIM syndrome?
What results in the neutrophil accumulation in the bone marrow in WHIM syndrome?
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What distinguishes congenital C3 deficiency from carrier status?
What distinguishes congenital C3 deficiency from carrier status?
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What test can be utilized to detect the respiratory burst in neutrophils?
What test can be utilized to detect the respiratory burst in neutrophils?
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Which of the following is NOT a result of mutations in the CXCR4 gene?
Which of the following is NOT a result of mutations in the CXCR4 gene?
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What condition is characterized by a defect in the ability of neutrophils to undergo a respiratory burst?
What condition is characterized by a defect in the ability of neutrophils to undergo a respiratory burst?
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What type of bacteria are associated with recurrent infections in congenital C3 deficiency?
What type of bacteria are associated with recurrent infections in congenital C3 deficiency?
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Which of the following statements about WHIM syndrome is FALSE?
Which of the following statements about WHIM syndrome is FALSE?
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Which of the following is an autosomal recessive condition?
Which of the following is an autosomal recessive condition?
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What is the main consequence of G-6-PD deficiency in leukocytes?
What is the main consequence of G-6-PD deficiency in leukocytes?
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Myeloperoxidase (MPO) deficiency primarily affects which types of white blood cells?
Myeloperoxidase (MPO) deficiency primarily affects which types of white blood cells?
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Lysosomal storage diseases (LSDs) result from mutations in genes coding for which of the following?
Lysosomal storage diseases (LSDs) result from mutations in genes coding for which of the following?
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Gaucher's disease is most commonly associated with a deficiency in which enzyme?
Gaucher's disease is most commonly associated with a deficiency in which enzyme?
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What characterizes Niemann-Pick's disease?
What characterizes Niemann-Pick's disease?
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Which clinical symptom is commonly associated with Gaucher's disease due to the presence of Gaucher cells in the bone marrow?
Which clinical symptom is commonly associated with Gaucher's disease due to the presence of Gaucher cells in the bone marrow?
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In which tissue do foam cells and sea-blue histiocytes typically accumulate in Niemann-Pick's disease?
In which tissue do foam cells and sea-blue histiocytes typically accumulate in Niemann-Pick's disease?
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How are lysosomal storage diseases classified?
How are lysosomal storage diseases classified?
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What is a common feature of lipid storage diseases or sphingolipidoses?
What is a common feature of lipid storage diseases or sphingolipidoses?
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What defines the autosomal recessive nature of Myeloperoxidase deficiency?
What defines the autosomal recessive nature of Myeloperoxidase deficiency?
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Which disorder is characterized by decreased nuclear segmentation and coarse chromatin clumping in leukocytes?
Which disorder is characterized by decreased nuclear segmentation and coarse chromatin clumping in leukocytes?
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What is a major defect associated with qualitative non-malignant leukocyte disorders?
What is a major defect associated with qualitative non-malignant leukocyte disorders?
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Which of these abnormalities involves large, darkly staining granules in granulocytes?
Which of these abnormalities involves large, darkly staining granules in granulocytes?
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Which genetic mutation is involved in May-Hegglin Anomaly?
Which genetic mutation is involved in May-Hegglin Anomaly?
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What clinical manifestations might occur in Homozygous Pelger-Huet Anomaly?
What clinical manifestations might occur in Homozygous Pelger-Huet Anomaly?
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Which disorder is characterized as a lysosomal storage disorder with defective leukocyte motility?
Which disorder is characterized as a lysosomal storage disorder with defective leukocyte motility?
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Hypersegmentation of neutrophils is a hallmark of which type of disorder?
Hypersegmentation of neutrophils is a hallmark of which type of disorder?
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What type of inheritance pattern is observed in Alder-Reilly Anomaly?
What type of inheritance pattern is observed in Alder-Reilly Anomaly?
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Study Notes
Non-Malignant Leukocyte Disorders
- These disorders are not caused by cancerous changes in immature blood cells
- Causes can be genetic or acquired
- They affect one or more lineages (neutrophils, lymphocytes, monocytes, eosinophils, and basophils)
- The number of circulating cells, their morphology, or both can be altered
- Many of these disorders correlate with significant clinical manifestations, though some are benign
Qualitative Non-Malignant Leukocyte Disorders
- These are characterized by morphological abnormalities involving neutrophils
- Defects in leukocyte motility/movement are possible
- Defective respiratory burst is a common issue
- Lysosomal storage disorders may occur, and inherited disorders of lymphocytes can be seen
- Defects in neutrophils are relevant (hypersegmentation, Alder-Reilly anomaly, May-Hegglin anomaly, Chédiak-Higashi syndrome, Pelger-Huet anomaly)
Pelger-Huet Anomaly (PHA)
- This is an autosomal dominant disorder characterized by distinctive coarse, decreased nuclear segmentation, and chromatin clumping
- Affects all leukocytes, but the morphological changes are most pronounced in mature neutrophils
- Mutations in the lamin B-receptor gene
- The lamin B receptor in the inner nuclear membrane is critical to leukocyte nuclear shape changes
- Heterozygous PHA is normal; homozygous PHA can lead to cognitive impairment, heart defects, and skeletal abnormalities
Alder-Reilly Anomaly
- A rare disorder marked by granulocytes (monocytes and lymphocytes) with large, darkly staining metachromatic cytoplasmic granules
- Initially noted in patients with gargoylism, it can also appear in otherwise healthy individuals
- Granulations are sometimes seen in mucopolysaccharidoses (MPSs)
May-Hegglin Anomaly
- An autosomal dominant disorder characterized by variable thrombocytopenia, giant platelets, and large Dohle body-like inclusions in neutrophils, eosinophils, basophils, and monocytes
- Results from a mutation in the MYH9 gene, disrupting myosin heavy chain type IIA production, affecting megakaryocyte maturation and platelet fragmentation
Chédiak-Higashi Syndrome
- A rare autosomal recessive immune dysregulation disease resulting from a CHS1 LYST gene mutation
- Affects many cell types, causing unusually large lysosomes containing dysfunctional granules
- Initial symptoms usually occur in infancy, marked by partial albinism and severe recurrent life-threatening bacterial infections
- Patients often have bleeding problems due to abnormal dense granules in platelets, and death typically occurs before age 10
Defective Leukocyte Motility/Movement
- Job's Syndrome: Abnormal chemotaxis/directional motility resulting in persistent boils and recurrent staphylococcal abscesses
- Lazy leukocyte syndrome: Cells fail to respond to inflammatory stimuli, but phagocytic and bactericidal activity remain normal
Leukocyte Adhesion Disorders (LADs)
- Rare autosomal recessive inherited conditions
- Characterized by an inability of neutrophils and monocytes to move from circulation to the site of inflammation (extravasation)
- Consequences include recurrent severe bacterial and fungal infections
- Hematopoietic stem cell transplant is the only curative treatment
- Types include LAD I, II, III, and others (e.g., Shwachman-Bodian-Diamond syndrome)
WHIM Syndrome
- Characterized by warts, hypogammaglobulinemia, infections and myelokathexis
- A defect in intrinsic and innate immunity related to mutations in the CXCR4 gene. The CXCR4 protein regulates the movement of white blood cells
- Neutrophils accumulate in the bone marrow (myelokathexis), resulting in low circulating neutrophils
- Patients experience recurrent bacterial infections and have a high susceptibility to human papillomavirus (HPV) infection, which can cause warts
Defective Respiratory Burst
- Chronic Granulomatous Disease (CGD): This is a rare condition caused by decreased ability of neutrophils to undergo the respiratory burst after phagocytosis of foreign organisms
- This results from mutations in genes involved in the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This leads to life-threatening catalase-positive bacterial and fungal infections
- Congenital C3 Deficiency: Defects result in the inability to produce a respiratory burst.
- G-6-PD Deficiency: Impairs the production of NADPH oxidase, leading to defects in bactericidal activity.
- Myeloperoxidase (MPO) Deficiency: Low or absent MPO in neutrophils and monocytes leads to reduced bactericidal killing activity
Lysosomal Storage Diseases (LSDs)
- These are due to inherited enzyme deficiencies leading to the buildup of undigested materials in lysosomes
- The effect is to cause cell dysfunction, cell death, and a range of clinical symptoms that affect cells containing lysosomes
- Classified according to the accumulated macromolecule
- Examples: Lipid storage disease/sphingolipidoses and mucopolysaccharidoses
Lipid Storage Disorders (Sphingolipidoses)
- Qualitative disorders involving monocytes and macrophages, which accumulate undegraded lipid products, expanding reticuloendothelial tissue
- Examples are Gaucher's disease and Niemann-Pick disease
Gaucher's Disease
- Most common of the lysosomal lipid storage diseases
- Autosomal recessive disorder related to a defect or deficiency in the catabolic enzyme beta-glucocerebrosidase
- Accumulation of sphingolipid glucocerebroside in macrophages throughout the body
- Includes osteoclasts in bone and microglia in the brain
- Bone marrow replacement leads to anemia and thrombocytopenia
- Pseudo-Gaucher cells may be present in bone marrow in some patients with specific cancers
Niemann-Pick Disease
- Results from a deficiency in the enzyme acid sphingomyelinase, leading to the accumulation of sphingomyelin in cellular lysosomes
- Three subtypes: A, B, and C
- Type A is an acute neuronopathic form, primarily affecting Eastern European Jewish populations
- Type C is a non-neuronopathic form, more common in individuals of Northern African descent
Other Lipid Storage Diseases
- Includes detailed descriptions of differing enzyme deficiencies and the resultant accumulated substances in relevant diseases.
Inherited Disorders of Lymphocytes
- Describes various B-cell and T-cell deficiencies including Bruton-Tyrosine Kinase deficiency, Common Variable Immunodeficiency, 22q11 Syndromes, Severe Combined Immunodeficiency (SCID) , X-linked SCID, Adenosine deaminase deficiency, and Wiskott-Aldrich syndrome
Quantitative Non-Malignant Leukocyte Disorders
- Covers conditions related to increased or decreased counts of specific leukocytes (e.g., neutrophils, eosinophils, basophils, monocytes, lymphocytes).
- Provides associated causes and conditions for each leukocyte category
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Description
Explore the complexities of non-malignant leukocyte disorders in this quiz. Learn about qualitative disorders, their causes, and significant clinical manifestations. Delve into specific conditions like Pelger-Huet anomaly and their impact on leukocyte morphology and function.
