Sphingolipidosis

Question 1

Where are ethanolamine plasmogens found?

Answer 1

myelin

Question 2

Where are choline plasmalogens found?

Answer 2

cardiac muscle

Question 3

Where does plasmogen synthesis occur?

Answer 3

in peroxisomes

Question 4

What are plasmogens derived from?

Answer 4

dihydroxyacetone phosphate

Question 5

What do phospholipids located in the cell membrane or in lysosomes do?

Answer 5

they degrade glycerophospholipids

Question 6

what does phospholipase A1 do?

Answer 6

it removes fatty acyl group on C1 of the glycerol backbone

Question 7

what does phospholipase A2 do?

Answer 7

it removes fatty acyl group on C2 of the glycerol backbone

Question 8

what does phospholipase C do?

Answer 8

it cleaves the bond joining C3 of glycerol moiety to phosphate

Question 9

What are shingolipids formed from?

Answer 9

ceramide

Question 10

Where and how is ceramide synthesized?

Answer 10

in the ER by condensation of serine and palmitoyl CoA

Question 11

What do sphingolipids do?

Answer 11

they serve in intracellular communication and as antigenic determinant of the ABO blood groups

Question 12

What are sphingolipids degraded by?

Answer 12

lysosomal enzymes

Question 13

What is the mode of inheritance for most sphingolipidoses?

Answer 13

autosomal recessive

Question 14

What are 4 constant features that are exhibited in these disorders?

Answer 14

• ceramide accumulation in cells, particularly neurons
• rate of synthesis of stored lipid is normal
• enzymatic defect is in the lysosomal degradation pathway of sphingolipds
• the extent to which the activity of the affected enzyme is decreased is similar in all tissues

Question 15

(1) autosomal recessive
(2) Defective Hexosaminidase A by mutation in HexA gene
(3) accumulation of ganglioside GM2
(4) common in Ashkenazi Jews
(5) progressive destruction of nerve cells in the brain and spinal cord, muscle atrophy, cherry red spot in retinoscopy, blind, deaf, unable to swallow

Answer 15

Tay-Sach’s Disease

Question 16

Without the alpha subunit, what happens with the beta subunit in Tay-Sachs Disease?

Answer 16

it can form active tetramers, named hexosaminidase B, which cleaves the glycolipid globoside., thus ganglioside GM@, but not globoside accumulates

Question 17

(1) autosomal recessive
(2) mutation in HexB gene
(3) inactivation of both hexosaminidase A and B
(4) accumulation of GM2 and globoside in the lysosomes
(5) mental retardation, blindness, muscular weakness

Answer 17

Sandhofff Disease

Question 18

(1) defective or absence of Sandhoff activator protein (required by hexosaminidase A)
(2) accumulation of GM2 ganglioside
(3) mental retardation, blindness, muscular weakness

Answer 18

Sandhoff Activator Disease

Question 19

(1) X-linked recessive
(2) deficiency of alpha-Galactosidase
(3) accumulation of globotriaosylceramide/ceramide trihexoside
(4) skin rash (angiokeratomas), kidney failure, cardiac complications, hypertension, cardiomyopathy
(5) Fabry crises: episodes of intesnse, excruciating burning pain felt initially in hands and feet, radiating to other parts of the body

Answer 19

Fabry’s Disease

Question 20

(1) autosomal recessive
(2) deficiency of glucocerebrosidase (beta-glucosidase)
(3) accumulation of glucocerebrosides in WBC, spleen, liver, kidney, lung, brain and bone marrow
(4) hepatosplenomegaly, anemia, thrombocytopenia, leukopenia, easily bruised, convulsions, hypertonia, dementia, ocular muscle apraxia
(5) “wrinkled tissue paper” looking cytoplasm of gaucher cells

Answer 20

Gaucher’s Disease

Question 21

(1) autosomal recessive
(2) complete absence of sphingomyelinase enzyme
(3) accumulation of sphingomyelin
(4) hepatosplenomegaly, ataxia, dysarthria, dysphagia, dystonia, supranuclear gaze palsy, dementia, seizures, cherry red spot retinoscopy, foam cells

Answer 21

Niemann-Pick Disease

Question 22

(1) autosomal recessive
(2) deficiency of ceramidase
(3) accumulation of ceramide in joints, CNS, throat, liver and other tissues
(4) subcutaneous nodules, tissue granulomas, joint pain, joint swelling, hoarseness of voice

Answer 22

Farber Disease

Question 23

What intermediates in glycolysis are important connections in carbohydrate and lipid metabolism?

Answer 23

glycerol phosphate and dihydroxyacetone phosphate (DHAP)