Genetics and Lysosomal Storage Disorders Quiz

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Questions and Answers

What is the primary consequence of having a pseudodeficiency allele in screening tests?

Prevention of GM2 ganglioside accumulation.

High levels of hex A activity.

Correct diagnosis of Tay-Sachs disease.

Incorrect diagnosis of being affected. (correct)

Which type of disease is I-cell disease classified as?

Autosomal recessive lysosomal storage disease. (correct)

Autosomal dominant disorder.

X-linked hereditary condition.

Mitochondrial genetic disorder.

What is one major effect of hex A pseudodeficiency alleles on prenatal diagnosis?

They allow for simpler genetic screening.

They complicate prenatal diagnosis. (correct)

They enhance accurate prenatal testing.

They are always related to Tay-Sachs mutations.

What characterizes the lysosomal enzymes in the cytoplasm of cultured skin fibroblasts from I-cell patients?

Numerous abnormal lysosomes or inclusions. Signup and view all the answers

What is the typical activity level of hex A in individuals with Tay-Sachs mutations?

Around 20% of control levels. Signup and view all the answers

What would be a potential supporting issue related to genetic screening programs for other diseases?

Possibility of false positives due to existing alleles. Signup and view all the answers

What defines housekeeping proteins?

They play essential roles in maintaining cell structure and function. Signup and view all the answers

Which of the following is true regarding the modification of hydrolases in I-cell disease patients?

They have elevated levels in body fluids. Signup and view all the answers

Which of the following statements about tissue-specific specialty proteins is true?

They contribute to the individuality of specific cells. Signup and view all the answers

What is the relationship between the expression of a protein and the site of disease?

Understanding where a protein is expressed can help understand disease pathogenesis. Signup and view all the answers

What common feature is noted among many lysosomal acid hydrolases?

They contain mannose residues that can be phosphorylated. Signup and view all the answers

Which of the following disorders is NOT mentioned as an example in the chapter?

Parkinson's disease Signup and view all the answers

Which general mechanism is discussed regarding how mutations cause genetic disease?

They can disrupt the synthesis or function of proteins. Signup and view all the answers

How many protein-coding genes do most human cell types express?

10,000 to 15,000 Signup and view all the answers

What role do lesser-known disorders play in the understanding of genetic diseases?

They are used to illustrate specific principles of disease mechanisms. Signup and view all the answers

Which statement describes the overall focus of the chapter?

It extends the examination of genetic disease mechanisms beyond hemoglobinopathies. Signup and view all the answers

What is the most common cause of familial hypercholesterolemia?

Mutations in the LDL receptor gene Signup and view all the answers

How is familial hypercholesterolemia inherited?

Autosomal semidominant Signup and view all the answers

What characterizes the homozygous form of familial hypercholesterolemia?

Earlier onset and more severe symptoms Signup and view all the answers

What is a common physical manifestation of familial hypercholesterolemia?

Xanthomas Signup and view all the answers

The increase in plasma LDL cholesterol in homozygotes is attributed to what?

Greater reduction in LDL receptors Signup and view all the answers

What are arcus corneae indicative of?

Cholesterol deposits around the cornea Signup and view all the answers

What risk is associated with elevated levels of LDL cholesterol?

Increased risk of heart attack and stroke Signup and view all the answers

What is the consequence for untreated homozygotes with familial hypercholesterolemia?

They may experience significant coronary heart disease in childhood. Signup and view all the answers

What is a known consequence of structural changes in α1-antitrypsin (α1AT)?

Formation of mutant α1AT polymers Signup and view all the answers

What percentage of the population are carriers of α1-antitrypsin deficiency?

4% Signup and view all the answers

How does smoking affect the survival of patients with α1-antitrypsin deficiency?

Decreases cumulative survival rates Signup and view all the answers

What is the prevalence of α1-antitrypsin deficiency in the population?

1 in 6700 persons Signup and view all the answers

Which group is likely to exhibit the worst survival rates with α1-antitrypsin deficiency?

Z/Z smokers Signup and view all the answers

What can be inferred about the α1AT alleles related to disease risk?

A dozen or so alleles increase disease risk Signup and view all the answers

What type of polymers does mutant α1-antitrypsin form due to structural changes?

Long beadlike necklaces Signup and view all the answers

Who are more likely to present with α1-antitrypsin deficiency?

Mostly M/M individuals Signup and view all the answers

What causes the clinical disease in patients with acute intermittent porphyria (AIP)?

Overload of residual PBG deaminase Signup and view all the answers

Which agents are known to induce the synthesis of ALA and PBG in carriers of AIP?

Drugs and chemicals Signup and view all the answers

What is the reduction level of PBG deaminase in patients affected by AIP?

50% of control levels Signup and view all the answers

In acute intermittent porphyria, which of the following is associated with clinically expressed symptoms?

Fasting and exposure to inducing agents Signup and view all the answers

What is the primary transport protein for cholesterol that is elevated in familial hypercholesterolemia?

Low-density lipoprotein (LDL) Signup and view all the answers

Which nervous systems are affected by the pathogenesis of the nervous system disease discussed?

Peripheral, autonomic, and central systems Signup and view all the answers

What condition is characterized by a greatly increased risk for myocardial infarction due to the affected LDL receptor?

Familial hypercholesterolemia Signup and view all the answers

What is one of the main neurological symptoms that manifests in patients with clinically expressed acute intermittent porphyria?

Seizures Signup and view all the answers

What process is stimulated by the activation of acyl coenzyme A : cholesterol acyl-transferase (ACAT)?

Cholesteryl esters storage Signup and view all the answers

What effect does an increase in intracellular cholesterol have on LDL receptors?

Decreases their synthesis Signup and view all the answers

How many different mutations have been identified in the LDLR gene?

More than 1100 Signup and view all the answers

What type of mutations accounts for 2% to 10% of LDLR alleles?

Structural rearrangements Signup and view all the answers

What is the majority type of mutation reported in the LDLR gene?

Single nucleotide substitutions Signup and view all the answers

What is a potential consequence of mutations in the LDLR gene?

Altered receptor function Signup and view all the answers

Which of the following statements is NOT true regarding the LDL receptor mutations?

Most mutations are functional. Signup and view all the answers

How does excess plasma cholesterol influence LDL receptor levels?

Inhibits receptor synthesis Signup and view all the answers

Study Notes

Genetic Disease

Genetic diseases are caused by abnormalities in gene and protein function.
Mutations can disrupt protein synthesis or function, leading to various diseases.
Proteins can be categorized as housekeeping proteins (expressed in all cells) or specialty proteins (expressed in specific cell types).
Mutations in tissue-specific proteins often result in tissue-specific diseases.
Mutations in housekeeping proteins can have limited tissue-specific effects.
Genetic redundancy, where an overlapping protein function exists in unaffected tissues, can minimize the impact of a mutated protein.

Enzymopathies

Enzymes are biological catalysts that convert substrates to products.
Hyperphenylalaninemias are inborn errors of metabolism that affect phenylalanine metabolism.
Phenylketonuria (PKU) is a severe form of hyperphenylalaninemia.
PKU results from mutations in the PAH gene.
PAH converts phenylalanine to tyrosine.
A diet low in phenylalanine is crucial for treating PKU.
Other hyperphenylalaninemias may result from defects in BH4 metabolism.
BH4 is a necessary cofactor for PAH activity.
Enzyme variants with residual activity cause milder hyperphenylalaninemia forms.
Loss-of-function mutations result in substrate accumulation or product deficiency.
Accumulated substrate or its derivatives may damage organs unrelated to the mutated enzyme.

Lysosomal Storage Diseases

Lysosomes contain hydrolytic enzymes that break down macromolecules.
Mutations in lysosomal enzymes cause a buildup of undegraded substrates within the cell.
Accumulating substrates disrupt normal cell function.
Tay-Sachs disease, a GM2 gangliosidosis, is a result of hexosaminidase A deficiency.
GM2 gangliosides accumulate in neurons causing neurodegeneration.
Clinical symptoms appear gradually in infancy.
Other lysosomal storage diseases have unique enzyme defects and varying clinical manifestations.
Some mutations lead to hypoglycosylation, resulting in defects in protein trafficking or structure.

Disorders of Structural Proteins

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked disorders involving dystrophin mutations.
Dystrophin is a structural protein essential for maintaining muscle membrane integrity.
Absence of dystrophin leads to progressive muscle damage and weakness.
DMD is typically severe with early onset and severe muscle weakness, unlike BMD which progresses more slowly.
Most DMD cases are due to deletions or point mutations in the dystrophin gene.
Genetic testing and carrier/prenatal genetic diagnosis are available for DMD.

Mitochondrial Diseases

Mitochondrial diseases can affect various organs, especially those with high energy demands.
Mutations in mitochondrial DNA (mtDNA) can cause these diseases.
mtDNA is maternally inherited, often resulting in heterogeneous presentations.
Heteroplasmy, the presence of both normal and mutated mtDNA, influences the clinical severity of symptoms.
Deletions/duplications are another source of mtDNA-linked disease.
Various clinical phenotypes reflect impacts on organs, tissues, etc.

Diseases Due to Repeat Expansions

Polyglutamine expansion in Huntington's disease leads to motor dysfunction or neurodegeneration.
Trinucleotide or tetranucleotide repeat expansions in other genes cause various neurological disorders (e.g., fragile X syndrome, Friedreich ataxia, myotonic dystrophy).
These disorders often exhibit anticipation, where symptoms appear earlier and/or are more severe in subsequent generations.

Other Disorders

Osteogenesis imperfecta is a group of genetic disorders causing skeletal fragility and abnormal bone development.
The disorders result from mutations in collagen genes, impacting normal collagen synthesis or structure.
Cystic fibrosis (CF), resulting from mutations in the CFTR gene, leads to thick mucus buildup in various organs, typically lungs and/or pancreas.

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Description

Test your knowledge on genetic screening, alleles, and lysosomal storage disorders such as I-cell disease and Tay-Sachs. This quiz covers the consequences of pseudodeficiency alleles, the role of housekeeping proteins, and characteristics of lysosomal enzymes. Dive into the complexities of genetic implications and enzyme activities in this informative quiz.