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83 Cards in this Set
- Front
- Back
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What is the most common form of genetic variation in the human genome?
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SNP
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What are the three categories of genetic change?
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1. Genome mutation
2. Chromosome mutation 3. Gene mutation |
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What type of inheritance is a delayed onset of the disease seen in?
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Autosomal dominant
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What are the two major non-enzymatic categories of proteins that are affected by an autosomal dominant mode of inheritance.
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1. Proteins involved in regulation of complex metabolic pathways subject to feedback
2. Key structural proteins |
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Name five characteristics of autosomal recessive inheritance.
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1. Phenotype is more uniform
2. Early onset 3. Affects enzymes 4. 100% penetrance 5. New mutations are rare |
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Which is more affected by a sex-linked disorder: hemizygous male or a heterozygous female?
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Hemizygous male
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What are the three consequences of defects in enzymes?
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1. Increased amount of substrate
2. Lack of essential end-product 3. Failure to inactivate tissue-damaging substrate |
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What is a common problem in substrate build-up and a lack of essential end-product?
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Build-up of toxic metabolites
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What is an example of a failure to inactivate tissue-damaging substrates?
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Alpha Anti-trypsin deficiency
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What is the prime example of a genetic enzyme deficiency that is unmasked when a certain drug is administered?
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Glucose-6-phosphate dehydrogenase deficiency - hemolysis after sulfa drugs are administered
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Marfan syndrome is a syndrome that mainly affects connective tissue of what areas?
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1. CV systen
2. Skeleton 3. Eyes |
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What is the defective protein in Marfan syndrome?
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Extracellular glycoprotein FBN-1
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What is another way to describe the mutation of fibrillin-1?
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Dominant negative
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A defect in FBN-2 is called what and how is it inherited?
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1. Congenital contractual arachnodactyly
2. AD |
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What is a hallmark sign of Marfan syndrome?
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Bilateral subluxation (up and out) of the lens - ectopia lentis
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What two major cardiovascular changes are seen in Marfan syndrome?
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1. Mitral valve prolapse
2. Dilation of the ascending aorta |
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What type of inheritance is seen in Marfan?
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AD
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What is the best characterized form of EDS? What is the defect in this variant? What is the MOI?
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1. Kyphoscoliosis
2. Lysyl hydroxylase 3. AR |
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The vascular variant of EDS involves what type of collagen?
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Type III (COL3A1)
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Three different mutations to COL3A1 can cause the vascular variant of EDS. How do the mutations function?
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1. Decreased synthesis of pre-procollagen
2. Decreased secretion of procollagen 3. Defective type III collagen produced (dominant negative) |
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Dermatosparaxis EDS is caused by what? What is the MOI?
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1. Defective procollagen-N-peptidase that cannot cleave Type I collagen (COL1A1 and COL1A2).
2. AR |
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Arthrochalasia EDS is caused by what? What is the MOI?
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1. Cleavage resistant COL1A1 and COL1A2
2. AD |
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What is the defect in Classical EDS? What is the MOI?
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1. The defect is in COL5A1 and COL5A2 (Type V collagen).
2. 30% to 50% AD |
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What is probably the most frequent Mendelian disorder? This results in the loss of what?
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1. Familial hypercholesterolemia
2. Feedback |
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What is the major source of LDL?
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IDL
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Once cholesterol is taken into the cell, what are the three results?
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1. Reduction in cholesterol synthesis - downregulation of HMG-CoA Reductase
2. Activation of cholesterol acetyltransferase - storage 3. Reduction in the production of LDL receptors |
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What are the five classes of mutations that can occur in familial hypercholestrolemia?
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1. Null allele
2. Receptor cannot leave the ER 3. Receptor has poor LDL binding ability 4. Receptor doesn't migrate to the coated pits 5. The receptor is not properly recycled |
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What is the most effective treatment for familial hypercholesterolemia?
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Use statins that inhibit HMG-CoA Reductase
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What are two properties of enzymes used in lysosomes
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1. They function in acidic enviroments
2. They are part of a special group of enzymes destined for the lysosome. |
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What is added to lysosomal enzymes that target them to the lysosome?
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Terminal mannose-6-phosphate groups
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What are six different ways a lysosomal storgae disorder can arise?
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1. Synthesis of an inactive protein that cross reacts with active enzyme
2. No terminal mannose-6-phosphate 3. Lack of enzyme activator or protection protein 4. Lack of substrate activator 5. Lack of a way to remove material from the lysosome 6. Inactive enzyme |
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What is the defective enzyme in Tay-Sachs disease? What accumulates?
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1. Hexosaminidase A - Alpha subunit
2. GM2 gangliosides |
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What do lysosomes look like histologically in Tay-Sachs?
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Lysosomes look like they are filled with onion-skin layers of membrane.
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What proliferates in Tay-Sachs?
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Microglia
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What actually causes a macular cherry spot?
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The accentuation of the normal color of the retina by the pale color of swollen ganglion cells.
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When are signs and symptoms first seen in Tay-Sachs disease?
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Six months
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When is death in Tay-Sachs?
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2-3 years of age
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What enzyme is involved in Sandoff disease?
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Beta sub-unit of hexosaminidase A
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What is the defect in the Niemann-Pick diseases?
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Defect in sphingomyelinase
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Which type of Niemann-Pick disease is the infantile form?
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Type A
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Which type of Niemann Pick disease only has organomegally?
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Type B
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What type of mutation causes the defect in Niemann-Pick disease?
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Missense mutation
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The lysosomes of what kind of cells are affected in Niemann-Pick disease?
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Mononuclear phagocyte system
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What is the special term for a histological finding in Niemann-Pick disease?
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Zebra bodies
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How often is a macular cherry spot seen in Niemann-Pick disease?
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1/3 to 1/2
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What is the most common type of Niemann-Pick disease?
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Type C
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What is the defect in Niemann-Pick type C?
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NPC-1 gene involved in cholesterol trafficking
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What is the most common presentation of Niemann-Pick type C?
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1. Ataxia
2. SNP 3. Psychomotor regression 4. Hepatosplenomegaly 5. Dysarthria |
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What is the most common lysosomal storage disorder? What is the defect in this disorder?
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1. Gaucher
2. Glucocerebrocidase |
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What are the three clinical sub-types of Gaucher?
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1. Type I - Chronic non-neuronopathic
2. Type II - Infantile - acute neuronopathic 3. Type III - intermediate |
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What types of symptoms are seen in Type I Gaucher?
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Splenic and skeletal disease
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What types of symptoms are seen in Type II Gaucher?
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CNS involvement due to no activity of glucocerebrocidase.
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What do Gaucher cells look like?
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Cytoplasm has a fibrillary appearance - that of crushed tissue paper
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Cytoplasm has a fibrillary appearance - that of crushed tissue paper
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Guacher Cell
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Why are there skeletal problems in Type I Gaucher?
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They are due to the fact that Gaucher cells infiltrate the bone marrow causing bone erosion.
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What is a Gaucher cell?
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Phagocytic cell with lots of infiltrated glucocerebroside.
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What is often seen in Type I Gaucher due to spleen involvement?
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Cytopenias
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What levels are elevated in macrophages in Gaucher disease?
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Chitotriosidase
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Mucopolysaccharidoses involve the accumulation of what?
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1. Heparan sulfate
2. Dermatn sulfate 3. Karatan sulfate 4. Chondroitin sulfate |
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The enzymes in mucopolysaccharidoses are supposed to cleave what?
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Terminal sugars
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Hurler syndrome is due to a deficiency of what enzyme?
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Alpha-1 iduronidase
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When does one usually die of Hurler syndrome?
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Age of 6
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What is seen in Hurler syndrome but is not seen in Hunter syndrome?
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Corneal clouding
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Hunter syndrome is due to a deficiency of what enzyme?
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Alpha-1 iduronidase - milder than Hurler
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What are the most common symptoms seen in MPS?
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1. Hepatosplenomegaly
2. Skeletal deformities 3. Valvular lesions 4. Subendothelial arterial deposits |
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What are the usual causes of death in MPSs?
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MI and cardiac decompression
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Balloon cells are associated with what type of diseases?
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MPSs
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How is Hunter syndrome inherited?
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X-linked
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What are the three major subtypes of glycogenoses?
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1. Hepatic - von Gierke
2. Myopathic - McArdle or Type VII 3. Systemic - Pompe |
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What is the deficient enzyme in von Gierke disease?
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Glucose-6-phosphotase
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What dominates the clinical picture in von Gierke disease?
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1. Heptatomegaly
2. Hypoglycemia |
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What is the deficient enzyme in McArdle's disease?
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Muscle phosphorylase
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What is the deficient enzyme in Type VII glycogenosis?
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PFK
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What dominates the clinical picture in McArdle and Type VII glycogenosis?
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1. Muscle weakness
2. Muscle cramping 3. Lack of exercise induced lactic acid build-up |
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What is the deficient enzyme in Pompe disease?
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Alpha-glucosidase (Acid maltase)
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Pompe disease usually results in what?
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Early death
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What is the deficient enzyme in Alkaptonuria? What builds up?
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1. Homogentisic oxidase
2. Homogentisic acid |
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What is a hallmark of Alkaptonuria?
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Black urine
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What is a major histological sign of Alkaptonuria?
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Ochronosis
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What is a consequence of ochronosis?
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Degeneration of articular joints
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What is the usual point of attack for ochronosis and when does it manifest?
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1. Intervertebral disc
2. 30's |
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Leber hereditary optic neuropathy is passed on how?
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Mitochondrial genes
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What is the main outcome of Leber hereditary optic neuropathy?
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Progressive bilateral loss of central vision between the ages of 15 to 35
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