Podcast
Questions and Answers
What is the main consequence of enzyme deficiencies in sphingolipidoses?
What is the main consequence of enzyme deficiencies in sphingolipidoses?
Which enzyme deficiency is primarily associated with Gaucher disease?
Which enzyme deficiency is primarily associated with Gaucher disease?
What pathology is particularly increased in individuals with MPO deficiency?
What pathology is particularly increased in individuals with MPO deficiency?
How are lysosomal storage disorders primarily characterized?
How are lysosomal storage disorders primarily characterized?
Signup and view all the answers
Which cellular components are primarily affected by the accumulation of glucocerebroside in Gaucher disease?
Which cellular components are primarily affected by the accumulation of glucocerebroside in Gaucher disease?
Signup and view all the answers
How many known disorders fall under the category of inborn errors of metabolism?
How many known disorders fall under the category of inborn errors of metabolism?
Signup and view all the answers
What type of genetic inheritance pattern is associated with Chédiak-Higashi syndrome?
What type of genetic inheritance pattern is associated with Chédiak-Higashi syndrome?
Signup and view all the answers
What type of genetic inheritance is associated with Gaucher disease?
What type of genetic inheritance is associated with Gaucher disease?
Signup and view all the answers
Which gene is mutated in Chédiak-Higashi syndrome?
Which gene is mutated in Chédiak-Higashi syndrome?
Signup and view all the answers
Which of the following symptoms is NOT commonly associated with Chédiak-Higashi syndrome?
Which of the following symptoms is NOT commonly associated with Chédiak-Higashi syndrome?
Signup and view all the answers
What is the chromosomal location of the GBA gene associated with Gaucher disease?
What is the chromosomal location of the GBA gene associated with Gaucher disease?
Signup and view all the answers
Which subgroup of diseases includes Chédiak-Higashi syndrome?
Which subgroup of diseases includes Chédiak-Higashi syndrome?
Signup and view all the answers
Which of the following is a common clinical manifestation of congenital neutropenia?
Which of the following is a common clinical manifestation of congenital neutropenia?
Signup and view all the answers
What is a characteristic feature in the blood films of patients with Chédiak-Higashi syndrome?
What is a characteristic feature in the blood films of patients with Chédiak-Higashi syndrome?
Signup and view all the answers
What is the main cause of increased susceptibility to infections in patients with Chédiak-Higashi syndrome?
What is the main cause of increased susceptibility to infections in patients with Chédiak-Higashi syndrome?
Signup and view all the answers
What is the typical absolute neutrophil count threshold for diagnosing congenital neutropenia?
What is the typical absolute neutrophil count threshold for diagnosing congenital neutropenia?
Signup and view all the answers
What is the primary genetic cause of SCN1?
What is the primary genetic cause of SCN1?
Signup and view all the answers
Which subtype of severe congenital neutropenia is associated with neurologic defects?
Which subtype of severe congenital neutropenia is associated with neurologic defects?
Signup and view all the answers
What inheritance pattern does SCN2 follow?
What inheritance pattern does SCN2 follow?
Signup and view all the answers
Which of the following provides no response to G-CSF?
Which of the following provides no response to G-CSF?
Signup and view all the answers
Which severe congenital neutropenia subtype is linked with facial dysmorphia and hypothyroidism?
Which severe congenital neutropenia subtype is linked with facial dysmorphia and hypothyroidism?
Signup and view all the answers
What is a common feature found in SCN mutations?
What is a common feature found in SCN mutations?
Signup and view all the answers
Which severe congenital neutropenia subtype is associated with 3-Methylglutaconic deficiency?
Which severe congenital neutropenia subtype is associated with 3-Methylglutaconic deficiency?
Signup and view all the answers
Which gene is affected in SCN5 that leads to various hematologic manifestations?
Which gene is affected in SCN5 that leads to various hematologic manifestations?
Signup and view all the answers
What symptom is commonly seen across all SCN subtypes?
What symptom is commonly seen across all SCN subtypes?
Signup and view all the answers
SCN4 is primarily associated with which type of genetic deficiency?
SCN4 is primarily associated with which type of genetic deficiency?
Signup and view all the answers
What characterizes a hematologic remission in acute leukemia?
What characterizes a hematologic remission in acute leukemia?
Signup and view all the answers
Which type of remission involves the absence of a cytogenetic defect?
Which type of remission involves the absence of a cytogenetic defect?
Signup and view all the answers
What does molecular remission specifically detect?
What does molecular remission specifically detect?
Signup and view all the answers
What is the objective of the consolidation phase in leukemia treatment?
What is the objective of the consolidation phase in leukemia treatment?
Signup and view all the answers
Which drug was the first rationally designed molecular targeted therapy for cancer?
Which drug was the first rationally designed molecular targeted therapy for cancer?
Signup and view all the answers
What does the t(9;22) translocation result in regarding CML?
What does the t(9;22) translocation result in regarding CML?
Signup and view all the answers
What role does imatinib play in the treatment of CML?
What role does imatinib play in the treatment of CML?
Signup and view all the answers
What is a common feature of targeted therapies in cancer treatment?
What is a common feature of targeted therapies in cancer treatment?
Signup and view all the answers
What is the primary reason Gaucher cells accumulate in the spleen, liver, and bone marrow?
What is the primary reason Gaucher cells accumulate in the spleen, liver, and bone marrow?
Signup and view all the answers
Which treatment option for Gaucher disease is considered to have the potential for a cure?
Which treatment option for Gaucher disease is considered to have the potential for a cure?
Signup and view all the answers
What characterizes true Gaucher cells under microscopic examination?
What characterizes true Gaucher cells under microscopic examination?
Signup and view all the answers
What is the hallmark of pseudo-Gaucher cells?
What is the hallmark of pseudo-Gaucher cells?
Signup and view all the answers
What is a common method used to confirm a diagnosis of Gaucher disease?
What is a common method used to confirm a diagnosis of Gaucher disease?
Signup and view all the answers
Which mutations are commonly screened for in patients suspected of having Gaucher disease?
Which mutations are commonly screened for in patients suspected of having Gaucher disease?
Signup and view all the answers
What is the consequence of untreated Gaucher disease in relation to blood cell production?
What is the consequence of untreated Gaucher disease in relation to blood cell production?
Signup and view all the answers
What staining methods are Gaucher cells known to positively react to?
What staining methods are Gaucher cells known to positively react to?
Signup and view all the answers
Study Notes
Chédiak-Higashi Syndrome (CHS)
- A rare autosomal recessive disease
- Classified as a familial hemophagocytic lymphohistiocytosis syndrome
- Characterized by immune dysregulation and hypopigmentation
- Caused by a mutation in the lysosomal trafficking regulator (LYST) gene on chromosome 1q42.3
- Mutation leads to giant fused cytoplasmic granules/inclusions in various cells, including leukocytes, platelets, fibroblasts, melanocytes, and other granulated cells in nerve tissue, kidney, and gastric mucosa
- Patients typically have cytopenias, particularly neutropenia
- Clinical manifestations include partial albinism, severe recurrent life-threatening bacterial infections, mild bleeding, easy bruising, and progressive neurologic impairment
- Genetic testing for mutations in LYST confirms the diagnosis
Congenital Neutropenia
- Absolute neutrophil count (ANC) less than 1.5 × 109/L
- Associated with a variety of nonmalignant conditions
- Decrease in neutrophils resulting from decreased production, increased destruction, or apoptosis
Severe Congenital Neutropenias (SCN)
- Ten subtypes listed (SCN1-SCN9 and SCNX)
- Mutations in the neutrophil elastase gene ELANE (causing SCN1) are responsible for 50% to 60% of all SCN cases
- Bone marrow examination in patients with SCN shows a maturation arrest in the neutrophil series at the myelocyte/promyelocyte stage and dysmorphic changes in neutrophilic cells
Sphingolipidoses
- Group of lysosomal storage disorders (LSDs)
- Functional deficiencies in enzymes needed for lysosomal breakdown of sphingolipids
- Harmful accumulation of various phospholipids in tissues
- Examples include Gaucher disease and Niemann-Pick disease
### Gaucher Disease (GD)
- Most common LSD
- Autosomal recessive disorder triggered by a defect or deficiency in the catabolic enzyme β-glucocerebrosidase
- Unmetabolized substrate sphingolipid glucocerebroside accumulates in the lysosomes of macrophages throughout the body
- Stems from a mutation in GBA located at 1q21-q22
- More than 400 pathogenic mutations
- Macrophages containing excess glucocerebroside accumulate in the spleen, liver, and bone marrow
- Gaucher cells are lysosome-engorged macrophages with eccentric nuclei and abundant fibrillar blue-gray cytoplasm with a striated or wrinkled appearance
- Stain positive with trichrome, aldehyde fuchsin, periodic acid-Schiff (PAS) and acid phosphatase
- In untreated patients, Gaucher cells infiltrate the hematopoietic space in bone resulting in anemia and thrombocytopenia
- All three types of GD have been associated with an increased risk for developing hematopoietic neoplasms, most frequently plasma cell (multiple) myeloma
- Treatment includes enzyme replacement therapy and substrate reduction therapy
- HSCT offers the potential for a cure but is not often used due to high treatment-related mortality
- Gene therapy, genome editing, and chaperone therapy are additional modalities being pursued
Pseudo-Gaucher Cells
- Seen in bone marrow specimens from patients with thalassemia, myeloid neoplasms, acute lymphoblastic leukemia, non-Hodgkin lymphoma, and plasma cell neoplasms
- Thought to result from increased cell turnover overwhelming the glucocerebrosidase enzyme
- Cause accumulation of glucosylceramide in macrophages
- Result from a relative rather than true decrease in enzyme
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on Chédiak-Higashi Syndrome and Congenital Neutropenia. This quiz covers the diseases' characteristics, genetic causes, clinical manifestations, and diagnostic methods. Perfect for students or healthcare professionals seeking to enhance their understanding of these rare syndromes.
