Lysosomal Storage Diseases

Question 1

Which lysosomal storage diseases are X-linked?

Answer 1

Danon, Fabry, and Hunter (Imagine a Hunter named Danon targeting an X as a Fabulous onlooker watches)

Question 2

What inheritance pattern do most lysosomal storage diseases follow?

Answer 2

They are all autosomal recessive except for the 3 that are X-linked

Question 3

Which lysosomal storage diseases occur more frequently in individuals of Ashkenazi Jewish decent?

Answer 3

Gaucher disease Tay-Sachs disease Niemann-Pick disease type A

Question 4

Tay-Sachs Disease

Answer 4

Deficiency: Beta-Hexosaminidase A

Accumulated Substrate: GM2 Ganglioside

Phenotype: Cherry-red macula + blindness + rapid/progressive neurodegeneration + delayed development + seizures

Notes: NO hepatosplenomegaly + whorled configuration within lysosomes composed of ONION-SKIN layers of membranes

Side note: Sandhoff’s disease is similar but with Beta-Hexosaminidase A AND B deficiency

Question 5

Nienmann-Pick Disease

Answer 5

Deficiency: Sphingomyelinase

Accumulated substrate: Sphingomyelin

Phenotype: Cherry-red macula + progressive neurologic deterioration + mental retardation + lung problems + hepatosplenomegaly

Notes: Foam Cells + Early Death

Question 6

Fabry Disease

Answer 6

Deficiency: Alpha-galactosidase A

Accumulated substrate: Globotriaosylceramide (ceramide trihexoside)

Phenotype: Affects PNS (pain in hands and feet) + angiokeratomas (small dark-red spots on skin) + GI problems + hypohidrosis + tinnitus + hearing loss

Memory aid: I FABRIcated a CERAmic GALaXy

Question 7

Gaucher Disease

Answer 7

Deficiency: Beta-glucocerebrosidase

Accumulated substrate: glucocerebroside

Phenotype: Hepatosplenomegaly + anemia + thrombocytopenia + lung disease + osteonecrosis + Erlenmayer flask distal femur deformity

Notes: Macrophages with “wrinkled paper appearance” –> Gaucher cells

Question 8

Farber Disease

Answer 8

Deficiency: Acid ceramidase

Accumulated substrate: Ceramide

Phenotype: Hoarse voice + weak cry + lipogranulomas (lipid deposition) + swollen/painful joins with progressive joint deformities + breathing problems + hepatosplenomegaly + developmental delay

Question 9

Krabbe Disease

Answer 9

Deficiency: Beta-Galactosylceramidase (galactocerebrosidase)

Accumulated substrate: Galactosylceramide (galactocerebroside)

Phenotype: Irritability + failure to thrive + progressive muscle weakness + unexplained fevers + stiff posture + slow mental/physical development + hearing loss + seizures

Notes: Globoid cells (large multinucleated cells)

Question 10

Danon Disease

Answer 10

Deficiency: Lysosome-associated membrane protein 2 (LAMP-2)

Accumulated substrate: Cytoplasmic debris and glycogen

Phenotype: Cardiomyopathy + Skeletal myopathy + mental retardation

Question 11

Hurler Disease (MPS I)

Answer 11

Deficiency: Alpha-L-Iduronidase

Accumulated substrate: Dermatan sulfate + heparan sulfate

Phenotype: Corneal clouding + dwarfism + progressive mental retardation + hepatosplenomegaly + coarse facial features + skeletal deformities (dysostosis multiplex) + large tongue

Notes: Appears normal at birth but with umbilical or inguinal hernia often present + death often by the age of 10 years d/t lung disease/infection or cardiac complications

Question 12

Hunter Disease (MPS II)

Answer 12

Deficiency: Iduronate-2-sulphatase (I2S)

Accumulated substrate: Dermatan sulfate and heparan sulfate

Phenotype: Progressive dteterioration + enlarged tongue + hearing loss + abnormal dentition + dysostosis multiplex + clawing of hands + hepatosplenomegaly + cardiomyopathy + short stature

Notes: NO corneal clouding (a hunter needs to see) + death usually in the first or second decade of life

Question 13

I-Cell disease (mucolipidosis II)

Answer 13

Deficiency: N-Acetylglucosamine-1-phosphotransferase

Accumulated substrate: Oligosaccharides + glycosaminoglycans (GAGs) + lipids

Phenotype: Hypotonia + developmental delay + limited mobility + clubfeet + thickened skin + short hands/fingers + possible heart valve problems + frequent respiratory infections

Notes: Present at birth or first few months of life + usually fatal before age 4

Question 14

Which lysosomal storage diseases present with cherry-red macula?

Answer 14

Tay-Sachs and Niemann-Pick

Question 15

Which lysosomal storage disease does NOT have hepatosplenomegaly?

Answer 15

Tay-Sachs

Question 16

Which lysosomal storage disease presents with Erlenmeyer flask deformities?

Answer 16

Gaucher

Question 17

Which lysosomal storage disease presents with angiokeratomas (small red/dark spots on skin)?

Answer 17

Fabry

Question 18

Which lysosomal storage disease presents with Corneal clouding?

Answer 18

Hurler

Question 19

Which lysosomal storage disease presents with lipogranulomas (lipid deposition)?

Answer 19

Farber

Question 20

Which lysosomal storage disease presents with tissue paper cytoplasm or macrophages with a “wrinkled paper” appearance?

Answer 20

Gaucer

Question 21

Which lysosomal storage disease presents with globoid cells (large multinucleated cells)?

Answer 21

Krabbe

Question 22

Which lysosomal storage disease presents with onion skin lysosome?

Answer 22

Tay-Sachs