Chédiak-Higashi & Congenital Neutropenia Quiz

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Questions and Answers

What is the main consequence of enzyme deficiencies in sphingolipidoses?

Enhanced immune response

Accumulation of sphingolipids (correct)

Increased enzyme activity

Destruction of lysosomes

Which enzyme deficiency is primarily associated with Gaucher disease?

Sphingomyelinase

Hexosaminidase A

α-galactosidase

β-glucocerebrosidase (correct)

What pathology is particularly increased in individuals with MPO deficiency?

Fungal infections (correct)

Viral infections

Parasitic infections

Bacterial infections

How are lysosomal storage disorders primarily characterized?

Buildup of toxic substances Signup and view all the answers

Which cellular components are primarily affected by the accumulation of glucocerebroside in Gaucher disease?

Macrophages and microglia Signup and view all the answers

How many known disorders fall under the category of inborn errors of metabolism?

1450 Signup and view all the answers

What type of genetic inheritance pattern is associated with Chédiak-Higashi syndrome?

Autosomal recessive Signup and view all the answers

What type of genetic inheritance is associated with Gaucher disease?

Autosomal recessive Signup and view all the answers

Which gene is mutated in Chédiak-Higashi syndrome?

LYST Signup and view all the answers

Which of the following symptoms is NOT commonly associated with Chédiak-Higashi syndrome?

Severe asthma attacks Signup and view all the answers

What is the chromosomal location of the GBA gene associated with Gaucher disease?

1q21-q22 Signup and view all the answers

Which subgroup of diseases includes Chédiak-Higashi syndrome?

Other nonlymphoid defects Signup and view all the answers

Which of the following is a common clinical manifestation of congenital neutropenia?

Non-malignant recurrent bacterial infections Signup and view all the answers

What is a characteristic feature in the blood films of patients with Chédiak-Higashi syndrome?

Presence of giant fused cytoplasmic granules Signup and view all the answers

What is the main cause of increased susceptibility to infections in patients with Chédiak-Higashi syndrome?

Genetic mutation in the LYST gene Signup and view all the answers

What is the typical absolute neutrophil count threshold for diagnosing congenital neutropenia?

Less than 1.5 × 10^9/L Signup and view all the answers

What is the primary genetic cause of SCN1?

ELANE gene mutation Signup and view all the answers

Which subtype of severe congenital neutropenia is associated with neurologic defects?

SCN3 Signup and view all the answers

What inheritance pattern does SCN2 follow?

Autosomal Dominant Signup and view all the answers

Which of the following provides no response to G-CSF?

SCN7 Signup and view all the answers

Which severe congenital neutropenia subtype is linked with facial dysmorphia and hypothyroidism?

SCN6 Signup and view all the answers

What is a common feature found in SCN mutations?

Myelocyte/pro-myeloid maturation arrest Signup and view all the answers

Which severe congenital neutropenia subtype is associated with 3-Methylglutaconic deficiency?

SCN9 Signup and view all the answers

Which gene is affected in SCN5 that leads to various hematologic manifestations?

VPS45 Signup and view all the answers

What symptom is commonly seen across all SCN subtypes?

Severe neutropenia Signup and view all the answers

SCN4 is primarily associated with which type of genetic deficiency?

G6PC3 deficiency Signup and view all the answers

What characterizes a hematologic remission in acute leukemia?

Normocellular bone marrow and no evidence of leukemia cells Signup and view all the answers

Which type of remission involves the absence of a cytogenetic defect?

Cytogenetic remission Signup and view all the answers

What does molecular remission specifically detect?

Absence of leukemia cell nucleic acid sequences Signup and view all the answers

What is the objective of the consolidation phase in leukemia treatment?

To further reduce the number of leukemia cells Signup and view all the answers

Which drug was the first rationally designed molecular targeted therapy for cancer?

Imatinib mesylate Signup and view all the answers

What does the t(9;22) translocation result in regarding CML?

Formation of the BCR::ABL1 gene fusion Signup and view all the answers

What role does imatinib play in the treatment of CML?

It inhibits the ABL1 domain of the fusion protein Signup and view all the answers

What is a common feature of targeted therapies in cancer treatment?

They specifically act on malignant cells Signup and view all the answers

What is the primary reason Gaucher cells accumulate in the spleen, liver, and bone marrow?

Accumulation of glucocerebroside Signup and view all the answers

Which treatment option for Gaucher disease is considered to have the potential for a cure?

Bone marrow transplant Signup and view all the answers

What characterizes true Gaucher cells under microscopic examination?

Eccentric nuclei with striated blue-gray cytoplasm Signup and view all the answers

What is the hallmark of pseudo-Gaucher cells?

Resulting from relative enzyme deficiency Signup and view all the answers

What is a common method used to confirm a diagnosis of Gaucher disease?

β-glucosidase activity test Signup and view all the answers

Which mutations are commonly screened for in patients suspected of having Gaucher disease?

N370S, 84GG, IVS2 +1G>A Signup and view all the answers

What is the consequence of untreated Gaucher disease in relation to blood cell production?

Anemia and thrombocytopenia Signup and view all the answers

What staining methods are Gaucher cells known to positively react to?

Trichrome, PAS, acid phosphatase 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

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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.