07b: Lysosomal Storage Diseases

Question 1

LSDs result from (excess/deficiency) in (X) enzymes, resulting in:

Answer 1

Deficiency;
X = lysosomal

Accumulation of insoluble/inert substances or metabolites within lysosome

Question 2

Most lysosomal storage disorders are inherited in (X) fashion. List key exception.

Answer 2

X = autosomal recessive

Hunter’s (X-linked recessive)

Question 3

Most lysosomal storage disorders are seen in (young/old) patient population.

Answer 3

Young (infants and small children)

Question 4

LSDs: typically involve enlargement of which organ(s)?

Answer 4

Liver and spleen (hepatosplenomegaly) (and lymph nodes)

Question 5

Heterophagy differs from autophagy in which key way?

Answer 5

Heterophay is breakdown of exogenous macromolecules; autophagy is turnover of intracellular organelles (endogenous)

Question 6

T/F: Neuronal damage is frequently associated with lysosomal storage diseases.

Answer 6

True

Question 7

LSDs: distribution of stored material (organs) is determined by which two factors?

Answer 7

1. Site where most material is found (gangliosides in brain)

2. Location of most degradation (RES/macrophages in nodes, spleen, liver)

Question 8

List the 3 major categories of macromolecules that accumulate in LSDs.

Answer 8

1. Sphingolipids
2. Mucopolysaccharides (proteoglycans)
3. Glycogen

Question 9

Sphingolipids are particularly abundant in which tissue type?

Answer 9

Brain and nervous tissue membranes

Question 10

Tay Sach’s Disease: missing enzyme is (X) and accumulated material is (Y).

Answer 10

X = hexosaminidase
Y = gangliosides

Question 11

Tay Sach’s Disease: (X) is major tissue affected. List some of the clinical manifestations.

Answer 11

X = neural and retina

Motor/mental deterioration, blindness, hypotonia (muscle flaccidity)

Question 12

“Cherry red spot” is clinical manifestation of which types of diseases?

Answer 12

Lysosomal storage diseases

Question 13

Tay Sachs: EM of lysosomes will appear like…

Answer 13

Whorled inclusions (layers of membrane); look like onion

Question 14

Niemann-Pick Disease: missing enzyme is (X) and accumulated material is (Y).

Answer 14

X = sphingomyelinase
Y = sphingomyelin (and cholesterol)

Question 15

Niemann-Pick Disease: Type A variant is (X)% of cases. What makes it different from Type B?

Answer 15

X = 75-80

1. CNS involvement
2. Progressive wasting and EARLY death (by age 3)

Question 16

Adult patient with liver enlargement and spleen enlargement to 10x normal size. Which LSD(s) could this be?

Answer 16

1. Niemann-Pick Disease (Type B)

2. Gaucher’s Type I

Question 17

EM of nerve cells with concentric “myelin” figures (Zebra bodies) indicative of which LSD(s)?

Answer 17

1. Niemann-Pick Disease

2. Hurlers Syndrome

Question 18

Gaucher Disease: missing enzyme is (X) and accumulated material is (Y).

Answer 18

X = Glucocerebrosidase
Y = Glucocerebrosides

Question 19

Gaucher Disease: Type 1 is (X)% of cases. How does it differ from Type 2?

Answer 19

X = 80 (“classic” type)

Non-neurotropic, adult type, only slightly decreased longevity

Question 20

Erlenmeyer flask deformity seen in which LSD?

Answer 20

Gaucher’s

Question 21

Gaucher’s disease: (low/high) platelet count, (low/high) WBCs, and (low/high) RBCs.

Answer 21

All low - sequestration; bone marrow replaced by Gaucher cells

Question 22

Mucopolysaccharidosis (MPS) I is also called (X) and the missing enzyme is (Y).

Answer 22

X = Hurlers Syndrome
Y = alpha-L-iduronidase

Question 23

Hurlers Syndrome: what’s the accumulated material?

Answer 23

Haparan and Dermatan sulfate

Question 24

Hurlers Syndrome: (X) is an important cause of death.

Answer 24

X = MI

Question 25

Which LSD has clinical manifestations that include cardiac valvular lesions, coronary artery deposits, and brain lesions?

Answer 25

Hurlers (and all MPS)

Question 26

T/F: Glycogenoses is deficiency of ANY enzyme involved in glycogen metabolism.

Answer 26

True

Question 27

Hepatic form of glycogenoses is (X) disease with (Y) missing enzyme.

Answer 27

X = Von Gierke's 
Y = glucose-6-phosphatase

Question 28

Von Gierke’s disease: which two symptoms dominate the clinical picture?

Answer 28

Hepatomegaly and hypoglycemia

Question 29

Pompe’s disease with (X) missing enzyme and (Y) accumulated material.

Answer 29

X = alpha-glucosidase (acid maltase)
Y = glycogen

Question 30

Pompe’s disease: which main symptom dominates the clinical picture?

Answer 30

Cardiomegaly (but muscle weakness and neuro symptoms also involved)