Podcast
Questions and Answers
Which of the following chromosomal abnormalities is NOT typically observed in cytogenetic analysis of Fanconi anemia cells?
Which of the following chromosomal abnormalities is NOT typically observed in cytogenetic analysis of Fanconi anemia cells?
- Dicentric chromosomes (correct)
- Translocations
- Chromatid breaks
- Chromatid gap
A researcher is investigating the genetic basis of Fanconi anemia (FA) using complementation analysis. What key principle underlies this approach?
A researcher is investigating the genetic basis of Fanconi anemia (FA) using complementation analysis. What key principle underlies this approach?
- FA is caused by epigenetic modifications rather than genetic mutations.
- If somatic cells from two FA patients with mutations in different genes are fused, the resulting hybrid cell may show a normal phenotype. (correct)
- Individuals with mutations in the same FA gene will show a corrected phenotype in somatic cell hybrids.
- FA results from mutations in a single, highly polymorphic gene.
What is the primary reason for the increased malignancy tendencies observed in individuals with Fanconi anemia (FA)?
What is the primary reason for the increased malignancy tendencies observed in individuals with Fanconi anemia (FA)?
- Compromised DNA repair mechanisms leading to increased chromatid abnormalities. (correct)
- Enhanced activity of oncogenes.
- Elevated levels of circulating inflammatory cytokines.
- Increased telomere length and genomic instability.
Which hematological finding is LEAST likely to be an initial presentation in a patient with Fanconi anemia?
Which hematological finding is LEAST likely to be an initial presentation in a patient with Fanconi anemia?
A child is suspected of having Fanconi anemia. Which of the following tests is most appropriate as the initial diagnostic step?
A child is suspected of having Fanconi anemia. Which of the following tests is most appropriate as the initial diagnostic step?
Which of the following is NOT typically part of the management strategy for Fanconi anemia (FA)?
Which of the following is NOT typically part of the management strategy for Fanconi anemia (FA)?
What is the most common cause of premature mortality in patients with Fanconi anemia (FA)?
What is the most common cause of premature mortality in patients with Fanconi anemia (FA)?
In the context of Fanconi anemia, what is the significance of chromosomal hypersensitivity to DNA cross-linking agents?
In the context of Fanconi anemia, what is the significance of chromosomal hypersensitivity to DNA cross-linking agents?
Why is long-term follow-up crucial for individuals with Fanconi anemia, even after undergoing hematopoietic stem cell transplantation?
Why is long-term follow-up crucial for individuals with Fanconi anemia, even after undergoing hematopoietic stem cell transplantation?
Individuals with Fanconi anemia (FA) are at an increased risk of developing certain types of cancer. Which of the following cancers is most commonly associated with FA?
Individuals with Fanconi anemia (FA) are at an increased risk of developing certain types of cancer. Which of the following cancers is most commonly associated with FA?
What is the underlying genetic defect that leads to Fanconi anemia (FA)?
What is the underlying genetic defect that leads to Fanconi anemia (FA)?
Which of the following populations has the LOWEST reported incidence of Fanconi Anemia?
Which of the following populations has the LOWEST reported incidence of Fanconi Anemia?
Which of the following best describes the inheritance pattern of Fanconi anemia?
Which of the following best describes the inheritance pattern of Fanconi anemia?
Which somatic abnormality is LEAST likely to be associated with Fanconi anemia ?
Which somatic abnormality is LEAST likely to be associated with Fanconi anemia ?
Which of the following statements about bone marrow failure in Fanconi anemia is most accurate?
Which of the following statements about bone marrow failure in Fanconi anemia is most accurate?
Which of the following abnormalities is commonly associated with Diamond-Blackfan anemia (DBA)?
Which of the following abnormalities is commonly associated with Diamond-Blackfan anemia (DBA)?
Which of the following is LEAST likely to be included in the management of Diamond-Blackfan anemia (DBA)?
Which of the following is LEAST likely to be included in the management of Diamond-Blackfan anemia (DBA)?
What is the most common presenting feature of Congenital Amegakaryocytic Thrombocytopenia?
What is the most common presenting feature of Congenital Amegakaryocytic Thrombocytopenia?
A 6-year-old child presents with macrocytic anemia, reticulocytopenia, and a normocellular bone marrow with a marked reduction in erythroid precursors. Which of the following conditions is most likely?
A 6-year-old child presents with macrocytic anemia, reticulocytopenia, and a normocellular bone marrow with a marked reduction in erythroid precursors. Which of the following conditions is most likely?
Which condition is characterized by total failure of white cells both lymphocyte and granulocyte and the infants with this condition die shortly after birth of overwhelming sepsis
Which condition is characterized by total failure of white cells both lymphocyte and granulocyte and the infants with this condition die shortly after birth of overwhelming sepsis
G-CSF (granulocyte colony-stimulating factor) is sometimes used in the management of congenital neutropenia. What is a significant potential risk associated with this treatment?
G-CSF (granulocyte colony-stimulating factor) is sometimes used in the management of congenital neutropenia. What is a significant potential risk associated with this treatment?
Which of the following laboratory findings is LEAST likely to be associated with Paroxysmal Nocturnal Hemoglobinuria?
Which of the following laboratory findings is LEAST likely to be associated with Paroxysmal Nocturnal Hemoglobinuria?
What is the underlying cause of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What is the underlying cause of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Which of the following clinical scenarios should prompt suspicion for Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Which of the following clinical scenarios should prompt suspicion for Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Which of the following proteins protect the red cell membrane from lysis by activated complement?
Which of the following proteins protect the red cell membrane from lysis by activated complement?
What is the role of Decay-Accelerating Factor (DAF/CD55) in the context of Paroxysmal Nocturnal Hemoglobinuria?
What is the role of Decay-Accelerating Factor (DAF/CD55) in the context of Paroxysmal Nocturnal Hemoglobinuria?
A patient with PNH is at increased risk for thrombosis. Which of the following best explains the cause of this increased risk?
A patient with PNH is at increased risk for thrombosis. Which of the following best explains the cause of this increased risk?
In Paroxysmal Nocturnal Hemoglobinuria (PNH), acute exacerbations of hemolysis are often associated with infections. Which pathway is primarily responsible for this process?
In Paroxysmal Nocturnal Hemoglobinuria (PNH), acute exacerbations of hemolysis are often associated with infections. Which pathway is primarily responsible for this process?
Which test definitively indicates the population of red cells sensitive to complement lysis?
Which test definitively indicates the population of red cells sensitive to complement lysis?
What is the primary goal of supportive measures in the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What is the primary goal of supportive measures in the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A patient with PNH presents with Budd-Chiari syndrome. Which of the following is the most likely underlying mechanism?
A patient with PNH presents with Budd-Chiari syndrome. Which of the following is the most likely underlying mechanism?
In the context of Paroxysmal Nocturnal Hemoglobinuria (PNH), what does the term 'clonal disorder' refer to?
In the context of Paroxysmal Nocturnal Hemoglobinuria (PNH), what does the term 'clonal disorder' refer to?
Which of the following conditions is LEAST commonly associated with the emergence of a PNH clone?
Which of the following conditions is LEAST commonly associated with the emergence of a PNH clone?
A young adult presents with hemolytic anemia, dark urine, and recurrent abdominal pain. Laboratory findings reveal low haptoglobin and elevated LDH. Further testing shows a reduced NAP score. What condition is most likely?
A young adult presents with hemolytic anemia, dark urine, and recurrent abdominal pain. Laboratory findings reveal low haptoglobin and elevated LDH. Further testing shows a reduced NAP score. What condition is most likely?
Why might serum ferritin levels be low in a patient with Paroxysmal Nocturnal Hemoglobinuria?
Why might serum ferritin levels be low in a patient with Paroxysmal Nocturnal Hemoglobinuria?
Given the complications associated with Paroxysmal Nocturnal Hemoglobinuria (PNH), which of the following is the MOST likely cause of mortality?
Given the complications associated with Paroxysmal Nocturnal Hemoglobinuria (PNH), which of the following is the MOST likely cause of mortality?
Which of the following tests assesses the population of red cells sensitive to complement lysis?
Which of the following tests assesses the population of red cells sensitive to complement lysis?
In the context of Pure Red Cell Aplasia, what is the significance of the term "maturation arrest"?
In the context of Pure Red Cell Aplasia, what is the significance of the term "maturation arrest"?
A researcher is investigating potential therapeutic targets in Fanconi anemia (FA). Which cellular process would offer the most direct target for intervention?
A researcher is investigating potential therapeutic targets in Fanconi anemia (FA). Which cellular process would offer the most direct target for intervention?
Which of the presented populations has the highest reported incidence of Fanconi Anemia?
Which of the presented populations has the highest reported incidence of Fanconi Anemia?
A 7-year-old child with Fanconi anemia (FA) is undergoing hematopoietic stem cell transplantation (HSCT). Despite successful engraftment, the patient develops squamous cell carcinoma at age 22. What explains this?
A 7-year-old child with Fanconi anemia (FA) is undergoing hematopoietic stem cell transplantation (HSCT). Despite successful engraftment, the patient develops squamous cell carcinoma at age 22. What explains this?
A researcher is investigating the genetic mutations responsible for Fanconi anemia (FA) in a cohort of patients. If the researcher performs complementation analysis, what outcome would indicate that two patients have mutations in different FA genes?
A researcher is investigating the genetic mutations responsible for Fanconi anemia (FA) in a cohort of patients. If the researcher performs complementation analysis, what outcome would indicate that two patients have mutations in different FA genes?
How do DNA cross-linking agents, such as diepoxybutane (DEB) and mitomycin C (MMC) help diagnose Fanconi Anemia (FA)?
How do DNA cross-linking agents, such as diepoxybutane (DEB) and mitomycin C (MMC) help diagnose Fanconi Anemia (FA)?
Why are individuals with Fanconi anemia (FA) more prone to developing acute myeloid leukemia (AML)?
Why are individuals with Fanconi anemia (FA) more prone to developing acute myeloid leukemia (AML)?
A newborn is suspected of having Fanconi anemia (FA) based on the presence of multiple congenital anomalies. Which of the following abnormalities would be least specific.
A newborn is suspected of having Fanconi anemia (FA) based on the presence of multiple congenital anomalies. Which of the following abnormalities would be least specific.
A bone marrow aspirate on a 6-year-old with suspected Fanconi anemia shows hypocellularity with increased macrophage activity and iron deposition. While awaiting definitive genetic testing, what immediate intervention is most appropriate?
A bone marrow aspirate on a 6-year-old with suspected Fanconi anemia shows hypocellularity with increased macrophage activity and iron deposition. While awaiting definitive genetic testing, what immediate intervention is most appropriate?
Considering the genetic diversity and multiple complementation groups associated with Fanconi anemia, which of the following statements is most accurate regarding mutation detection strategies?
Considering the genetic diversity and multiple complementation groups associated with Fanconi anemia, which of the following statements is most accurate regarding mutation detection strategies?
A 19-year-old female with known Fanconi anemia desires fertility preservation prior to undergoing hematopoietic stem cell transplantation. What is her prognosis?
A 19-year-old female with known Fanconi anemia desires fertility preservation prior to undergoing hematopoietic stem cell transplantation. What is her prognosis?
What clinical scenario should raise the highest suspicion for Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What clinical scenario should raise the highest suspicion for Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A patient with confirmed Paroxysmal Nocturnal Hemoglobinuria (PNH) experiences an acute exacerbation of hemolysis during a severe bacterial infection. By which pathway is this process primarily mediated?
A patient with confirmed Paroxysmal Nocturnal Hemoglobinuria (PNH) experiences an acute exacerbation of hemolysis during a severe bacterial infection. By which pathway is this process primarily mediated?
What is the importance CD55 in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What is the importance CD55 in Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A young male presents with dark urine especially in the morning, fatigue, and a history of recurrent abdominal pain. Initial labs show evidence of hemolytic anemia. Which of the following additional findings would strongly support the diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
A young male presents with dark urine especially in the morning, fatigue, and a history of recurrent abdominal pain. Initial labs show evidence of hemolytic anemia. Which of the following additional findings would strongly support the diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What is the underlying genetic defect that leads to Paroxysmal Nocturnal Hemoglobinuria (PNH)?
What is the underlying genetic defect that leads to Paroxysmal Nocturnal Hemoglobinuria (PNH)?
Flashcards
Fanconi Anemia (FA)
Fanconi Anemia (FA)
The most common inherited disorder associated with bone marrow failure. It is well-characterized along with Dyskeratosis congenita.
Fanconi Anemia (FA) Definition
Fanconi Anemia (FA) Definition
A rare genetic disease resulting in impaired response to DNA damage, leading to increased cancer risk, especially acute myeloid leukemia.
Fanconi Anemia Incidence
Fanconi Anemia Incidence
The incidence varies but falls approximately within 1 in 100,000 to 1 in 350,000 live births.
Genetics of Fanconi's Anemia
Genetics of Fanconi's Anemia
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FA cellular characteristic
FA cellular characteristic
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Chromosomal Abnormalities in FA
Chromosomal Abnormalities in FA
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FA causal genes
FA causal genes
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Hematological Features of FA
Hematological Features of FA
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Bone Marrow in FA
Bone Marrow in FA
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Marrow Failure in FA
Marrow Failure in FA
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Front line diagnostic test for Fanconi's Anemia (FA)
Front line diagnostic test for Fanconi's Anemia (FA)
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Treatments for Fanconi Anemia (FA)
Treatments for Fanconi Anemia (FA)
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Cumulative Incidence of FA
Cumulative Incidence of FA
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Pure Red Cell Aplasia
Pure Red Cell Aplasia
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Pure Red Cell Aplasia Classification
Pure Red Cell Aplasia Classification
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Many cases are sporadic but families with autosomal recessive and autosomal dominant inheritance have been described
Many cases are sporadic but families with autosomal recessive and autosomal dominant inheritance have been described
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Classical manifestation of Diamond-Blackfan Anaemia
Classical manifestation of Diamond-Blackfan Anaemia
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Dysmorphisms of Diamond-Blackfan Anaemia.
Dysmorphisms of Diamond-Blackfan Anaemia.
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Reticular dysgenesis
Reticular dysgenesis
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kostmann's syndrome
kostmann's syndrome
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Congenital amegakaryoctic thrombocytopaenia
Congenital amegakaryoctic thrombocytopaenia
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Paroxysmal nocturnal haemoglobinuria
Paroxysmal nocturnal haemoglobinuria
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Symptoms of Paroxysmal nocturnal haemoglobinuria
Symptoms of Paroxysmal nocturnal haemoglobinuria
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Diagnosis of Paroxysmal nocturnal haemoglobinuria
Diagnosis of Paroxysmal nocturnal haemoglobinuria
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Study Notes
- Fanconi anaemia is the most common inherited disorder associated with bone marrow failure
- Dyskeratosis congenita is another well-characterized inherited disorder associated with bone marrow failure.
- Fanconi Anaemia (FA) is a rare genetic disease causing impaired response to DNA damage
- Most individuals affected by FA develop cancer, especially acute myeloid leukaemia, at an earlier age
Disease Characteristics
- FA affects many parts of the body
- Individuals with FA develop bone marrow failure in almost 90% of cases
- Congenital defects, affecting skin, arms, head, eyes, kidneys, and ears occur in 60-75% of FA cases
- Developmental disabilities, such as short stature and endocrine disorders, are associated with FA
Discovery
- Guido Fanconi, a Swiss paediatrician, first described FA in 1927 in Switzerland
- He described familial aplastic anemia in 3 brothers with short stature, microcephaly, internal strabismus, genital hypoplasia, and abnormal skin pigmentation
Epidemiology
- The incidence of FA varies between 1 per 100,000 to 250,000 live births
- Some sources estimate the incidence as 1 per 350,000 live births
- Heterozygote frequency varies with founding mutations.
- FA occurs in 1 in 83 people in the Afrikaans population in South Africa.
- It occurs in 1 in 100 people in Ashkenazi Jews
- FA occurs in 1 in 64 to 1 in 70 people in Spanish gypsies compared to 1 in 189 in the general population
- In Europe and the United States, the estimated incidence is 1 in 300
- Approximately 1,000 persons are affected worldwide
- The male:female ratio of the disease presentation is 1.2:1
Somatic Abnormalities in FA
- Low birth weight is a somatic abnormality of FA
- Microcephaly is a somatic abnormality of FA
- Microphthalmia is a somatic abnormality of FA
- Horseshoe kidney is a somatic abnormality of FA
- Strabismus is a somatic abnormality of FA
- Short stature is a somatic abnormality of FA
- Pelvic kidney is a somatic abnormality of FA
- Cryptorchism is a somatic abnormality of FA
- Mental retardation is a somatic abnormality of FA
- Vascular malformations is a somatic abnormality of FA
- Growth hormone deficiency is a somatic abnormality of FA
- Skeletal abnormalities of thumbs and radii are somatic abnormalities of FA
- Patches skin hyperpigmentation (café au lait)is a somatic abnormality of FA.
Genetics of FA
- FA results from a defect in clusters of proteins responsible for DNA repair
- Majority of FA patients develop cancer, bone marrow failure, and congenital defects as a result of genetic defects in DNA repair proteins
- FA cells are characterized by chromosomal hypersensitivity to DNA cross-linking agents.
- Cytogenetic analysis reveals chromosomal abnormalities (chromatid gap, chromatid breaks, reduplication, exchanges, translocations) in FA cells
- These abnormalities are particularly present when cells are exposed to DNA cross-linking agents like alkylating agents, mitomycin C, and diepoxybutane
- Chronic villus cells exhibit sensitivity to clastogens, allowing for antenatal diagnosis
- There is considerable genetic heterogeneity in FA
- Complementation analysis of somatic cell hybrids suggests the existence of several FA genes, grouped into eight groups
Complementation Groups in FA
- FA-A has a chr location of 16q24.3, protein of 1455 and accounts for 65–70 %FA patients with a mutation ide of >120
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