Glycobiology in Human Disease II

Question 1

Patients with Mucopolysaccharidoses suffer from

Answer 1

Skeletal and extracellular matrix deformities

Question 2

Clinical diagnosis of a mucopolysaccharidosis is confirmed by measuring the patient’s levels of

Answer 2

Lysosomal hydrolases

Question 3

The mucopolysaccharidoses are hereditary diseases caused by a deficiency of any one of the lysosomal hydrolases normally involved in the degradation of

Answer 3

Heparin sulfate and/or Dermatan sulfate

Question 4

Progressive disorders characterized by accumulation of glycosaminoglycans in various tissues, causing a range of symptoms, such as skeletal and extracellular matrix deformities, and mental retardation

Answer 4

Mucopolysaccharidoses

Question 5

Children who are homozygous for any one of these diseases are apparently normal at birth, and then

Answer 5

Gradually deteriorate

Question 6

All mucopolysaccharidoses are autosomal recessive diseases except

Answer 6

Hunter Syndrome (X-linked)

Question 7

Incomplete lysosomal degradation of glycosaminoglycans results in the presence of oligosaccharides in the

Answer 7

Urine

Question 8

These fragments can be used to diagnose the specific mucopolysaccharidosis by identifying the structure present on the nonreducing end of the

Answer 8

Oligosaccharide

Question 9

That is because the residue at the nonreducing end would have been the substrate for the

Answer 9

Missing enzyme

Question 10

Bone marrow and cord blood transplants have been used to treat

Answer 10

Hurler and Hunter syndromes

Question 11

Caused by a defect in alpha-L-iduronidase

-an inherited autosomal recessive disorder

Answer 11

Hurler syndrome

Question 12

Characteristic features of this disease including coarsening of the facial features, corneal clouding, and hepatosplenomegaly appear around age 2 in affected individuals

Answer 12

Hurler syndrome

Question 13

Due to thickening of respiratory secretions, individuals with Hurler syndrome are prone to

Answer 13

Recurrent infections

Question 14

Patients with Hurler syndrome have a markedly shortened lifespan, often dying before the age of

Answer 14

10

Question 15

Caused by a defect in iduronate sulfatase

Answer 15

Hunter Syndrome

Question 16

In contrast to Hurler syndrome, Hunter syndrome is inherited in an

Answer 16

X-linked recessive pattern

Question 17

Additionally, Hunter syndrome typically occurs

Answer 17

Later in life

Question 18

Additionally, Hunter syndrome typically occurs later in life that Hurler syndrome and does not have the cardinal feature of

Answer 18

Corneal clouding

Question 19

Has the key features of intellectual disability, coarse facial features, and short stature

Answer 19

Hunter Syndrome

Question 20

Results from failure of the body to be able to cleave the alpha 1,4 linkage

Answer 20

Pompe Disease

Question 21

The defective degradation of glycogen in the lysosomes seen in Pompe disease is caused by the lack of which enzyme?

Answer 21

Lysosomal acid alpha-glucosidase (acid maltase)

Question 22

The classic infantile form of Pompe disease causes

Answer 22

Cardiomegaly, hypotonia, hepatomegaly, and death before 2 due to cardiorespiratory failure

Question 23

A heterogeneous group of molecules that are hydrophobic

Answer 23

Lipids

Question 24

Allow for fats to be transported both extracellularly and intracellularly

Answer 24

Lipoproteins

Question 25

The main constituent of body fat in the human body

Answer 25

TAGs

Question 26

Serve as a major source of energy for the body

Answer 26

Lipids

Question 27

Lipids can be classified as either -Depending on their structural backbone

Answer 27

Glycerolipids or Sphingolipids

Question 28

The major consitituents of all cell membranes

Answer 28

Glycerophospholipids

Question 29

Serve to help anchor proteins in the membrane and can play a role in intracellular signaling (e.g., epinephrine activates phospholipase –C)

Answer 29

Glycerophospholipids

Question 30

Other unique functions of glycerophospholipids include playing a role in the composition of

Answer 30

Bile, lipoproteins, and lung surfactant

Question 31

What are the three most abundant glycerophospholipids? -primary function is structural role in membranes

Answer 31

Phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine

Question 32

Glycerophospholipids are synthesized in all cells except for

Answer 32

Mature erythrocytes

Question 33

Synthesized in the smooth ER and transported to the Golgi body to be sent to membranes or secreted

Answer 33

Glycerophospholipids

Question 34

This compound can be synthesized de novo from preexisting choline; however, this de novo synthesis is not sufficient for our body’s needs

Answer 34

Phosphatidylcholine (Lecithin)

Question 35

Can be obtained as an essential dietary nutrient in foods such as fish, eggs, broccoli, peanut butter, and milk chocolate

Answer 35

Phosphatidylcholine (Lecithin)

Question 36

Serves as a structural component of membranes, a mild detergent in bile, and as part of a surfactant in the small alveoli of the lungs

Answer 36

Lecithin

Question 37

Impaired production of lecithin can allow for solubilization of hydrophobic compounds in bile, leading to

Answer 37

Gallstones

Question 38

Inadequate production of lecithin allows for alveoli to collapse in the lungs due to too much

Answer 38

Surface tension

Question 39

This collapse is commonly seen in premature infants who are born before there is enough

Answer 39

Lecithin produced

Question 40

Inadequate production of lecithin allows for alveoli to collapse, this is referred to as

Answer 40

Respiratory distress syndrome

Question 41

Exogenous administration of cortisol to a mother can help increase

Answer 41

Surfactant (Lecithin) production

Question 42

Used to assess for adequate levels of surfactant -Can be obtained by amniocentesis

Answer 42

Lecithin : Sphingomyelin ratio (L:S)

Question 43

What is an adequate L:S?

Answer 43

Greater than 2

Question 44

What L:S value indicates risk for respiratory distress?

Answer 44

Less than 1.5

Question 45

Serves as the structural backbone of sphingolipids

Answer 45

Sphingosine

Question 46

An example of a sphingophospholipids in the body that plays an integral role in the nervous system

Answer 46

Sphingomyelin

Question 47

As evidenced by its name, sphingomyelin is an important component of the myelin nerve fibers that allow for quick conduction of

Answer 47

Electrical signals

Question 48

The immediate precursor to sphingomyelin is

Answer 48

Ceramide

Question 49

Catalyzes the breakdown of sphingomyelin into ceramide and phosphatidylcholine

Answer 49

Sphingomyelinase

Question 50

Catalyzes the breakdown of ceramide into sphingosine and FFA

Answer 50

Ceramidase

Question 51

If there is a deficiency of the enzyme sphingomyelinase. As a result, sphingomyelin will build up at toxic levels resulting in a clinical syndrome manifested by

Answer 51

Severe neurological damage, liver enlargement, and premature death

Question 52

Deficiency of the enzyme sphingomyelinase. As a result, sphingomyelin will build up at toxic levels resulting in a clinical syndrome manifested by severe neurological damage, liver enlargement, and premature death

Answer 52

Niemann-Pick disease

Question 53

Very severe disease with <1% sphingomyelinase activity -more frequent in Ashkenazi Jewish population, death during infanthood

Answer 53

Type A Neimann Pick

Question 54

Less severe form of the disease with 5% or more sphingomyelinase activity -Life extended to adulthood

Answer 54

Type B Neimann Pick

Question 55

A type of sphingolipid that contains both carbohydrates and lipids

Answer 55

Glycolipid

Question 56

A key component in the production of glycolipids

Answer 56

Ceramide

Question 57

Can be combined with UDP-sugars to form various glycolipid precursors

Answer 57

Ceramide

Question 58

The degradation of glycolipids follows the classic format of

Answer 58

Last on, first off

Question 59

A type of lipid molecule that function to provide stability and protection to the plasma membrane lipid bilayer

Answer 59

Sphingolipids

Question 60

In a normal individual, synthesis and degradation of glycosphingolipids are balanced, so that the amount of these compounds present in membranes is

Answer 60

Constant

Question 61

Sphingolipidoses typically have an effect on -due to accumulation of toxic biochemical entities

Answer 61

Neuronal function

Question 62

A specific lysosomal hydrolytic enzyme is deficient in each

Answer 62

Sphingolipidoses

Question 63

Each sphingolipidoses is characterized by the accumulation of a single -Dependent on which enzyme is deficient

Answer 63

Sphingolipid

Question 64

The disorders are progressive and, although many are fatal in childhood, extensive phenotypic variability is seen leading to the designation of different clinical types

Answer 64

Sphingolipidoses

Question 65

The sphingolipidoses are autosomal recessive diseases, except for

Answer 65

Fabry disease (X-linked)

Question 66

The incidence of the sphingolipidoses is low in most populations, except for -Like Niemann-Pick disease, show a high frequency in the Ashkenazi Jewish population

Answer 66

Gaucher and Tay-Sachs diseases

Question 67

A specific sphingolipidosis can be diagnosed by measuring enzyme activity in cultured fibroblasts or peripheral leukocytes, or by analysis of

Answer 67

DNA

Question 68

Shell-like inclusion bodies are seen in histological examination of

Answer 68

Tay-Sachs

Question 69

A wrinkled tissue paper appearance of the cytosol is seen in

Answer 69

Gaucher disease

Question 70

In Gaucher disease, macrophages become engorged with

Answer 70

Glucocerebroside

Question 71

Globosides accumulate in the vascular endothelial lysosomes of the brain, heart, kidneys, and skin in

Answer 71

Fabry Disease

Question 72

Treated by recombinant human enzyme replacement therapy

Answer 72

Gaucher and Fabry disease

Question 73

Has also been treated by bone marrow transplantation, and by substrate reduction therapy through pharmacological reduction of glucosylceramide, the substrate for the deficient enzyme

Answer 73

Gaucher DIsease

Question 74

This disease state is commonly found in Jewish populations of Eastern European decent

Answer 74

Tay-Sachs

Question 75

The pathogenesis of Tay-Sachs involves an accumulation of ganglionucleosides secondary to a deficient enzyme important for normal breakdown. The deficient enzyme is

Answer 75

B-Hexosaminidase A

Question 76

A lack of this important enzyme in the breakdown pathway leads to an accumulation of toxic

Answer 76

Gangliosides

Question 77

This accumulation of gangliosides results in the progressive deterioration of

Answer 77

Nerve Cells

Question 78

Over time, patients develop progressive neurological dysfunction including poor muscle tone, seizures, nystagmus, ataxia, hyperreflexia, pathological reflexes, and loss of vision

Answer 78

Tay-Sachs

Question 79

A “cherry-red spot” (although not diagnostic) can be seen on eye examination with

Answer 79

Tay-Sachs

Question 80

This disease state is a group of inherited metabolic disorders characterized by an autosomal recessive pattern

Answer 80

Niemann-Pick Disease

Question 81

The disease involves defective breakdown of sphingolipids resulting in toxic accumulations of sphingomyelin

Answer 81

Niemann-Pick Disease

Question 82

Sphingomyelin is a component of the cell membrane that is typically broken down in

Answer 82

Lysosomes

Question 83

Sphingomyelin accumulates in lysosomes when we are missing the enzyme

Answer 83

Sphingomyelinase

Question 84

Characterized by cells with a “foamy” appearance, due to the accumulation of lipids (fat) within the lysosome

Answer 84

Niemann-Pick Disease

Question 85

In Niemann-Pick disease, sphingomyelin buildup is especially prominant in macrophages in the

Answer 85

Spleen and liver (results in hepatosplenomegaly)

Question 86

Many of the neurological findings in Niemann-Pick disease are similar to those of

Answer 86

Tay-Sachs

Question 87

Also shows the cherry-red spot

Answer 87

Niemann-Pick disease

Question 88

The prototype of macrophage storage disorder is

Answer 88

Gaucher disease

Question 89

An autosomal recessive disease caused by a deficiency in glucocerebrocidase

Answer 89

Gaucher disease

Question 90

Tissues most affected by Gaucher disease are those whose lysosomes store the

Answer 90

Glucocerebroside

Question 91

Lysosomes are critical to the function of

Answer 91

Macrophages

Question 92

Bone marrow, the liver, lungs, spleen, and brain are affected by

Answer 92

Gaucher disease

Question 93

Also affected by Gaucher disease since lysosome activity is critical to their function -bone cells

Answer 93

Osteoclasts

Question 94

Symptoms include hepatosplenomegaly, pancytopenia, severe pain in bones and joints (particularly in the hips and knees), osteoporosis, avascular necrosis of bones, and potential neurological dysfunction

Answer 94

Gaucher Disease

Question 95

Diagnosis can be made with measurement of glucocerebrosidase activity in peripheral leukocytes

Answer 95

Gaucher disease

Question 96

Treatment for Gaucher disease is available with

Answer 96

Intravenous recombinant glucocerebrosidase

Question 97

Yet another rare, autosomal recessive neurodegenerative disorder. The hallmark features involve myelin loss and the presence of globoid bodies within the white matter

Answer 97

Krabbe Disease

Question 98

The structural changes seen in Krabbe disease occur due to an inherited deficiency of the lysosomal enzyme

Answer 98

B-galactocerebrosidase

Question 99

Without this enzyme, the body cannot break down myelin successfully, which gives rise to a host of neurological symptoms

Answer 99

B-galactocerebrosidase

Question 100

From gross neurological deficits to optic atrophy, there is no single presentation of

Answer 100

Krabbe Disease