Genetic Disorders and Mechanisms Quiz

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Questions and Answers

What enzyme is absent in Lesch-Nyhan syndrome, and what is the consequence of this absence?

HGPRT is absent, leading to de novo purine synthesis impairment and increased uric acid production.

Describe the genetic mechanism that leads to β-thalassemia.

It involves mutations at splice sites or promoter sequences, which can result in retained introns in mRNA.

What leads to microsatellite instability in Lynch syndrome?

Failure of mismatch repair during the S phase of the cell cycle causes microsatellite instability.

What is the effect of the defect in N-acetylglucosaminyl-1-phosphotransferase in I-cell disease?

It leads to failure in mannose residues phosphorylation in the Golgi, resulting in cellular debris accumulation in lysosomes. Signup and view all the answers

What mutation is responsible for Marfan syndrome and its effects on the body?

A mutation in the FBN1 gene on chromosome 15 causes defective fibrillin, which normally forms a sheath around elastin. Signup and view all the answers

What is the primary defect in X-linked (Bruton) agammaglobulinemia?

A defect in the BTK gene prevents B-cell maturation, resulting in absent B cells in peripheral blood. Signup and view all the answers

Describe the mechanism that leads to Graft-versus-host disease.

Graft-versus-host disease occurs due to a type IV hypersensitivity reaction where donor T cells attack host cells due to HLA mismatch. Signup and view all the answers

What is the relationship between CD4+ T cells and cytokine release?

CD4+ T cells are responsible for releasing cytokines that facilitate various immune responses, including activating other immune cells. Signup and view all the answers

What characterizes Chronic Granulomatous Disease (CGD) in terms of neutrophil function?

CGD is characterized by a defect in NADPH oxidase, leading to reduced reactive oxygen species and impaired respiratory burst in neutrophils. Signup and view all the answers

How does Tetanospasmin affect neurotransmission?

Tetanospasmin prevents the release of inhibitory neurotransmitters like GABA and glycine from Renshaw cells, leading to muscle spasms. Signup and view all the answers

Explain the importance of the LFA-1 integrin in leukocyte adhesion deficiency.

The LFA-1 integrin (CD18) is crucial for phagocyte migration and chemotaxis, and its defect leads to impaired immune responses. Signup and view all the answers

What happens during a hemolytic transfusion reaction?

Hemolytic transfusion reactions occur due to a type II hypersensitivity reaction against donor RBCs, typically involving ABO antigens. Signup and view all the answers

What causes the pulmonary hypertension associated with Eisenmenger syndrome?

Eisenmenger syndrome occurs due to an uncorrected left-to-right shunt that results in increased pulmonary blood flow, remodeling of vasculature, and eventual right-to-left shunting. Signup and view all the answers

How does the C. difficile toxin contribute to pseudomembranous colitis?

Toxins A and B released by C. difficile damage enterocytes, leading to inflammation and watery diarrhea, characteristic of pseudomembranous colitis. Signup and view all the answers

What is the mechanism by which botulism toxin affects the neuromuscular junction?

Botulism toxin cleaves SNARE proteins, inhibiting the release of the neurotransmitter acetylcholine at the neuromuscular junction. Signup and view all the answers

What genetic mutation is associated with Angelman syndrome?

A deletion or mutation of the paternal allele affecting the UBE3A gene on chromosome 15. Signup and view all the answers

Describe the genetic cause of cystic fibrosis.

Cystic fibrosis is caused by an autosomal recessive ΔF508 deletion in the CFTR gene on chromosome 7. Signup and view all the answers

What is the main consequence of a dystrophin gene mutation in Duchenne muscular dystrophy?

The main consequence is myonecrosis due to loss of the anchoring protein dystrophin to the extracellular matrix. Signup and view all the answers

How does the CTG trinucleotide repeat expansion affect patients with myotonic dystrophy?

It leads to abnormal expression of the myotonin protein kinase, causing myotonia. Signup and view all the answers

What is the pathological mechanism behind fragile X syndrome?

Fragile X syndrome is caused by CGG trinucleotide repeat expansion in the FMR1 gene leading to hypermethylation. Signup and view all the answers

What nutritional deficiency leads to Bitot spots in vitamin A deficiency?

Bitot spots are caused by a deficiency in vitamin A, resulting in squamous metaplasia of conjunctival epithelial cells. Signup and view all the answers

Explain the effect of thiamine deficiency in Wernicke encephalopathy.

Thiamine deficiency results in impaired glucose breakdown, leading to ATP depletion worsened by glucose infusion. Signup and view all the answers

What is the primary consequence of hereditary fructose intolerance?

The primary consequence is accumulation of fructose-1-phosphate due to aldolase B deficiency, leading to phosphate depletion. Signup and view all the answers

Describe the primary feature of classic galactosemia.

Classic galactosemia results from a deficiency in galactose-1-phosphate uridyltransferase, causing accumulation of toxic substances. Signup and view all the answers

What are the mechanisms involved in type I hypersensitivity reactions?

Type I hypersensitivity involves antigen cross-linking with IgE on mast cells, causing degranulation and release of histamine. Signup and view all the answers

What is the impact of the mutation in COL1A1 and COL1A2 genes in osteogenesis imperfecta?

It leads to a defect in type 1 collagen formation, affecting the stability and strength of bones. Signup and view all the answers

What are the consequences of impaired copper absorption and transport in Menkes disease?

It results in reduced lysyl oxidase activity, which impairs collagen cross-linking. Signup and view all the answers

Explain the genetic basis of Prader-Willi syndrome.

It is caused by uniparental disomy or imprinting that silences the paternal gene. Signup and view all the answers

How does the defect in N-acetylglucosaminyl-1-phosphotransferase affect lysosomal function in I-cell disease?

It leads to a failure in the phosphorylation of mannose residues, causing cellular debris accumulation in lysosomes. Signup and view all the answers

What role does the FBN1 gene play in Marfan syndrome?

The FBN1 gene mutation leads to defective fibrillin, which normally provides elasticity to connective tissues. Signup and view all the answers

What gene mutation is associated with the loss of dystrophin in Duchenne muscular dystrophy?

Dystrophin gene frameshift mutations. Signup and view all the answers

In myotonic dystrophy, what genetic alteration is responsible for the condition?

CTG trinucleotide repeat expansion in the DMPK gene. Signup and view all the answers

What is the primary cause of cataracts and peripheral neuropathy in diabetes mellitus?

Intracellular sorbitol accumulation due to lack of sorbitol dehydrogenase. Signup and view all the answers

What deficiency leads to Pellagra in malignant carcinoid syndrome?

Tryptophan diversion towards serotonin synthesis. Signup and view all the answers

What is the major consequence of C1 esterase inhibitor deficiency in hereditary angioedema?

Unregulated activation of kallikrein and increased bradykinin levels. Signup and view all the answers

What leads to recurrent Neisseria bacteremia in patients?

Terminal complement deficiencies affecting C5–C9. Signup and view all the answers

What cellular process is disrupted in Wernicke encephalopathy following thiamine deficiency?

Impaired glucose breakdown leads to ATP depletion. Signup and view all the answers

What triggers histamine release in type I hypersensitivity reactions?

Antigen cross-links IgE on mast cells. Signup and view all the answers

What metabolic defect is associated with hereditary fructose intolerance?

Aldolase B deficiency leading to fructose-1-phosphate accumulation. Signup and view all the answers

What is the consequence of hypermethylation in fragile X syndrome?

Reduced expression of the FMR1 gene. Signup and view all the answers

What is the primary defect in Hyper-IgM syndrome?

Defective CD40L on T helper cells leads to a class switching defect. Signup and view all the answers

What causes the neutrophils' impaired function in Chronic Granulomatous Disease?

A defect in NADPH oxidase results in reduced reactive oxygen species production. Signup and view all the answers

How does the α toxin from gas gangrene contribute to tissue damage?

The α toxin degrades phospholipids, leading to myonecrosis. Signup and view all the answers

What is the mechanism behind the tissue damage caused by Shiga toxin in hemolytic uremic syndrome?

Shiga toxin inactivates the 60S ribosome, leading to decreased protein synthesis and cytokine release. Signup and view all the answers

In DiGeorge syndrome, what is primarily affected due to the 22q11 microdeletion?

The development of the 3rd and 4th branchial pouches is impaired. Signup and view all the answers

How does a lack of effective vaccine for N. gonorrhoeae relate to antigenic variation?

N. gonorrhoeae undergoes antigenic variation of pilus proteins, preventing effective immune response. Signup and view all the answers

What is the primary immune response in tuberculoid leprosy, and what symptoms does it cause?

A Th1 immune response leads to mild symptoms and effective granuloma formation. Signup and view all the answers

What is the consequence of E-cadherin dysfunction in cancer invasion?

Dysfunction of E-cadherin leads to loss of intercellular junctions, facilitating tumor invasion. Signup and view all the answers

What characterizes the immune response in graft-versus-host disease?

Donor T cells attack host cells due to HLA mismatch, indicating a type IV hypersensitivity reaction. Signup and view all the answers

What occurs due to the retrograde transport of rabies virus in neuronal cells?

The rabies virus binds to ACh receptors, utilizing retrograde transport to invade the CNS. Signup and view all the answers

Study Notes

Lesch-Nyhan Syndrome

Deficiency in hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
Increased de novo purine synthesis and uric acid production

β-Thalassemia

Mutations in splice sites or promoter sequences within the β-globin gene
Result in retained introns in mRNA

Lynch Syndrome

Failure of mismatch repair during the S phase of the cell cycle
Leads to microsatellite instability

I-Cell Disease

Deficiency in N-acetylglucosaminyl-1-phosphotransferase
This enzyme is responsible for phosphorylating mannose residues in the Golgi apparatus
Results in failure of lysosomal enzymes to be properly targeted to lysosomes
Leads to accumulation of cellular debris in lysosomes

Osteogenesis Imperfecta

Defect in type 1 collagen
This defect results from mutations in the COL1A1 and COL1A2 genes
Leads to an inability to form triple helices

Menkes Disease

Defective ATP7A protein
This protein is responsible for copper absorption and transport
Leads to impaired lysyl oxidase activity
Decreased collagen cross-linking

Marfan Syndrome

Mutation in the FBN1 gene on chromosome 15
This gene encodes fibrillin which forms a sheath around elastin
Results in defective fibrillin

Prader-Willi Syndrome

Caused by uniparental disomy or imprinting
This leads to silencing of the maternal gene
Disease is expressed when the paternal allele is deleted or mutated

Angelman Syndrome

Silenced paternal gene
Leads to mutation, lack of expression, or deletion of UBE3A on the maternal chromosome 15

Cystic Fibrosis

Autosomal recessive disorder
Caused by a ΔF508 deletion in the CFTR gene on chromosome 7
This gene encodes an ATP-gated chloride channel
Results in impaired chloride transport in the lungs, gastrointestinal tract, and sweat glands

Duchenne Muscular Dystrophy

Caused by frameshift mutations in the dystrophin gene
This gene encodes a protein that anchors the cytoskeleton to the extracellular matrix
Leads to loss of dystrophin and myonecrosis

Myotonic Dystrophy

Caused by a CTG trinucleotide repeat expansion in the DMPK gene
This gene encodes a myotonin protein kinase
Results in abnormal expression of myotonin protein kinase and myotonia

Fragile X Syndrome

Caused by a CGG trinucleotide repeat expansion in the FMR1 gene
This gene encodes a protein involved in mRNA translation
Results in hypermethylation and silencing of the FMR1 gene

Bitot Spots in Vitamin A Deficiency

Deficiency in vitamin A leads to impaired epithelial cell differentiation
This results in squamous metaplasia

Wernicke Encephalopathy in Alcoholic Patient Given Glucose

Thiamine deficiency in alcoholic patients
This impairs glucose breakdown and ATP depletion
Glucose infusion worsens the situation

Pellagra in Malignant Carcinoid Syndrome

Tryptophan is diverted towards serotonin synthesis by the tumor.
This results in a deficiency of B3, which is derived from tryptophan

Kwashiorkor

Protein malnutrition
Leads to decreased oncotic pressure and edema
Impaired apolipoprotein synthesis and fatty liver changes

Lactic Acidosis, Fasting Hypoglycemia, Hepatic Steatosis in Alcoholism

Ethanol metabolism increases the NADH/NAD+ ratio
This disrupts normal metabolic pathways

Aspirin-Induced Hyperthermia

Aspirin increases the permeability of the mitochondrial membrane
This uncouples oxidative phosphorylation and decreases ATP production

Hereditary Fructose Intolerance

Deficiency in aldolase B
This enzyme is necessary for fructose metabolism
Results in accumulation of fructose-1-phosphate which inhibits glycogenolysis and gluconeogenesis

Classic Galactosemia

Deficiency in galactose-1-phosphate uridyltransferase
This enzyme is involved in galactose metabolism
Results in accumulation of toxic metabolites such as galactitol

Cataracts, Retinopathy, Peripheral Neuropathy in Diabetes Mellitus

Lens, retina, and Schwann cells lack sorbitol dehydrogenase
This leads to accumulation of sorbitol within these cells
Sorbitol is a sugar alcohol that is osmotic
This accumulation causes osmotic damage to these tissues

Recurrent Neisseria Bacteremia

Deficiency in terminal complement components (C5-C9)
This leads to failure of the membrane attack complex (MAC) formation
MAC is required for lysis of bacteria

Hereditary Angioedema

Deficiency in C1 esterase inhibitor
This inhibitor prevents the uncontrolled activation of the kallikrein-kinin system
Results in unregulated activation of kallikrein and the release of bradykinin
Bradykinin is a potent vasodilator that causes edema

Paroxysmal Nocturnal Hemoglobinuria

Mutation in the PIGA gene
This gene is required for the formation of glycosylphosphatidylinositol (GPI) anchors
GPI anchors are necessary for complement inhibitors (DAF/CD55, MIRL/CD59) to attach to red blood cells
Absence of these inhibitors leads to complement-mediated intravascular hemolysis

Type I Hypersensitivity

Immediate reaction: antigen cross-links IgE on mast cells, leading to degranulation and release of histamine and tryptase
Late reaction: mast cells secrete chemokines and leukotrienes, attracting eosinophils and causing inflammation and tissue damage

Type II Hypersensitivity

Antibodies bind to cell-surface antigens
This leads to cell destruction, inflammation, and cellular dysfunction

Type III Hypersensitivity

Antigen-antibody complexes activate complement and attract neutrophils

Type IV Hypersensitivity

Cell-mediated response
No antibodies are involved
CD8+ T cells directly kill target cells
CD+ T cells release cytokines

Acute Hemolytic Transfusion Reaction

Type II hypersensitivity reaction against donor red blood cells
Typically due to ABO blood group incompatibility

X-Linked (Bruton) Agammaglobulinemia

Defect in the BTK gene
This gene encodes a tyrosine kinase critical for B-cell development
Results in a lack of B-cell maturation and absent B cells in peripheral blood
All immunoglobulin classes are absent

DiGeorge Syndrome

22q11 microdeletion
This microdeletion leads to failure of the 3rd and 4th branchial pouches to develop
These pouches contribute to the development of the thymus and parathyroid glands

Hyper-IgM Syndrome

Defect in CD40L on Th cells
This defect prevents class switching of immunoglobulins

Leukocyte Adhesion Deficiency (Type 1)

Defect in LFA-1 integrin (CD18)
This integrin is essential for leukocyte adhesion and migration
Leads to impaired phagocyte migration and chemotaxis

Chédiak-Higashi Syndrome

LYST mutation
This mutation affects microtubule function
Leads to defective phagosome-lysosome fusion

Chronic Granulomatous Disease

NADPH oxidase defect
This enzyme is responsible for producing reactive oxygen species (ROS) during the respiratory burst in neutrophils
Leads to impaired bacterial killing

Candida Infection in Immunodeficiency

Candida infections are often seen in patients with impaired T cell or granulocyte function
Impaired T cell function leads to local candidiasis
Impaired granulocyte function leads to systemic candidiasis

Graft-versus-Host Disease

Type IV hypersensitivity reaction
Occurs when donor T cells attack host cells
This is typically due to HLA mismatch between the donor and recipient

Recurrent Staphylococcus aureus, Serratia, and Burkholderia cepacia Infections in CGD

Catalase + organisms can degrade hydrogen peroxide (H2O2)
H2O2 is essential for the myeloperoxidase system to produce microbicidal products
Patients with chronic granulomatous disease cannot produce H2O2
This allows catalase + organisms to survive and cause recurrent infections

Hemolytic Uremic Syndrome

Caused by Shiga or Shiga-like toxins
These toxins inactivate the 60S ribosomal subunit
This leads to inhibition of protein synthesis and cell death
Also leads to cytokine release and inflammation

Tetanus

Caused by tetanus toxin (tetanospasmin)
This toxin blocks the release of inhibitory neurotransmitters (GABA and glycine) from Renshaw cells
Leads to uncontrolled muscle contraction

Botulism

Caused by botulinum toxin
This toxin is a protease that cleaves SNARE proteins
SNARE proteins are essential for neurotransmitter release
Results in paralysis

Gas Gangrene

Caused by Clostridium perfringens
This bacteria produces alpha toxin
Alpha toxin is a phospholipase/lecithinase that degrades phospholipids in cell membranes
Leads to myonecrosis

Toxic Shock Syndrome, Scarlet Fever

Both caused by toxins produced by Staphylococcus aureus and Streptococcus pyogenes
These toxins bind to the beta region of the T cell receptor (TCR) outside of antigen binding site
This activates T cells and promotes the release of pro-inflammatory cytokines like IL-1, IL-2, IFN-gamma, and TNF-alpha

Shock and Disseminated Intravascular Coagulation (DIC) by Gram-Negative Bacteria

Gram-negative bacterial lipopolysaccharide (LPS) activates macrophages through TLR4/CD14 complex
LPS also activates the complement system
This leads to the release of tissue factor, which promotes coagulation

Prosthetic Device Infection by Staphylococcus epidermidis

Staphylococcus epidermidis produces biofilms
Biofilms are a protective layer of bacteria that can resist antibiotics and host defenses
These biofilms can form on prosthetic devices and cause infections

Endocarditis Secondary to Streptococcus sanguinis

Streptococcus sanguinis produces dextrans, which bind to fibrin-platelet aggregates
These aggregates often form on damaged heart valves
Streptococcus sanguinis can then colonize these aggregates and cause endocarditis

Pseudomembranous Colitis Secondary to Clostridium difficile

Clostridium difficile produces Toxins A and B
These toxins damage enterocytes leading to watery diarrhea
This can lead to pseudomembranous colitis

Diphtheria

Caused by Corynebacterium diphtheriae
This bacterium produces diphtheria toxin
Diphtheria toxin inhibits protein synthesis by ADP-ribosylating elongation factor 2 (EF-2)

Virulence of Mycobacterium tuberculosis

Cord factor activates macrophages and promotes granuloma formation
It also induces the release of TNF-alpha
Sulfatides on the bacterial surface inhibit phagolysosomal fusion

Tuberculoid Leprosy

Characterized by a Th1 immune response
Leads to milder symptoms

No Effective Vaccine for Neisseria gonorrhoeae

Neisseria gonorrhoeae exhibits antigenic variation of its pilus proteins
This makes it difficult to develop a vaccine that can target a variety of strains

Cystitis and Pyelonephritis by Escherichia coli

Escherichia coli expresses fimbriae (P pili), which allow the bacteria to attach to the urinary tract

Pneumonia and Neonatal Meningitis by Escherichia coli

Escherichia coli expresses a K capsule, which helps the bacteria evade the host's immune system

Chlamydiae Resistance to Beta-Lactam Antibiotics

Chlamydiae lack classic peptidoglycan
This is because they have reduced muramic acid content
This makes them resistant to beta-lactam antibiotics, which target peptidoglycan synthesis

Influenza Pandemics

Caused by RNA segment reassortment
This leads to antigenic shift
Reassortment occurs when two different influenza viruses infect the same cell
The resulting virus may have a new combination of genes, leading to a new pandemic strain

Influenza Epidemics

Caused by mutations in the hemagglutinin and neuraminidase genes
This leads to antigenic drift
These mutations occur gradually over time and cause smaller-scale epidemics

CNS Invasion by Rabies Virus

Rabies binds to acetylcholine receptors (AChRs)
It then travels retrogradely to the central nervous system
It does this by using the motor protein dynein

HIV Infection

HIV binds to CD4 receptors on macrophages
It also binds to CCR5 on macrophages (early infection) or CXCR4 on T cells (late infection)
Binding of HIV to these receptors allows the virus to enter and infect these cells

Granuloma Formation

Macrophages present antigens to CD4+ T cells
This leads to secretion of IL-12 by macrophages
This stimulates the differentiation of CD4+ T cells into Th1 cells
Th1 cells secrete interferon-gamma (IFN-gamma), which activates macrophages
Macrophages then form granulomas to contain the infection

Limitless Replicative Potential of Cancer Cells

Cancer cells reactivate telomerase
This allows them to maintain and lengthen their telomeres
Telomeres are protective caps at the ends of chromosomes
They prevent chromosome shortening and aging
The reactivation of telomerase allows cancer cells to divide indefinitely

Tissue Invasion by Cancer Cells

Cancer cells downregulate E-cadherin function
This disrupts intercellular junctions
This allows cancer cells to move away from the primary tumor
Cancer cells also secrete metalloproteinases
These enzymes degrade the basement membrane and extracellular matrix proteins
This allows cancer cells to invade surrounding tissues and metastasize

Persistent Truncus Arteriosus

Failure of the aorticopulmonary septum to form
This results in a single great artery that arises from the heart

D-Transposition of the Great Arteries

Failure of the aorticopulmonary septum to spiral
This results in the aorta arising from the right ventricle and the pulmonary artery arising from the left ventricle

Tet Spells in Tetralogy of Fallot

Tetralogy of Fallot is a heart defect that includes a ventricular septal defect (VSD), pulmonary stenosis, overriding aorta, and right ventricular hypertrophy
Crying, fever, or exercise can worsen the pulmonary stenosis
This leads to right-to-left shunting across the VSD
Squatting increases systemic vascular resistance (SVR)
This decreases right-to-left shunting and improves cyanosis

Eisenmenger Syndrome

Uncorrected left-to-right shunting
This leads to increased pulmonary blood flow
This causes remodeling of the pulmonary vasculature, resulting in pulmonary hypertension
Pulmonary hypertension leads to right ventricular hypertrophy (RVH)
This causes a reversal of the shunt, leading to right-to-left shunting and cyanosis

Atherosclerosis

Begins with endothelial cell dysfunction
This leads to accumulation of macrophages and LDL in the arterial wall
Macrophages engulf LDL, resulting in foam cell formation
This causes fatty streaks
Smooth muscle cell migration and extracellular matrix deposition leads to fibrous plaque formation
This ultimately leads to complex atheromas

Thoracic Aortic Aneurysm

Caused by cystic medial degeneration
This is a weakening of the aortic media
This can lead to dilation and aneurysm formation

Myocardial Infarction

Caused by a rupture of a coronary artery atherosclerotic plaque
This results in acute thrombosis, blocking blood flow to the heart
This can lead to myocardial cell death and infarction