Lysosomal Storage Disorders Flashcards
What is the deficient enzyme in Hurler Syndrome?
Iduronidase
Which substrates accumulate in Hurler Syndrome?
Dermatan Sulfate
Heparan Sulfate
What diagnostic method do you use for Hurler Syndrome?
Fibroblast assay
In Hurler Syndrome, what can be found in the urine?
Glycosaminoglycans
What is the deficiency enzyme in Hunter Syndrome?
Iduronate Sulfatase
Which is milder, Hunter or Hurler syndrome?
Hunter
What is one distinguishing characteristic between patients with Hunter syndrome and Hurler syndrome?
Hunter Syndrome = NO corneal clouding
What are some features of patients with Hurler syndrome?
Course facial features Short stature Developmental delay Hepatosplenomegaly restricted joint mobility Corneal Clouding
What are some features of patients with Hunter Syndrome?
Course facial features
hepatosplenomegaly
mild to moderate mental retardation
What are sphingolipids?
group of complex lipids containing sphingosine as alcohol
What makes up ceramide?
Sphingosine + fatty acid = ceramide
What are the two classes of Sphingolipids?
Glycosphingolipids
Sphingophospholipids
What do glycosphingolipids contain?
A carbohydrate moiety linked to ceramide
What do Sphingophospholipids contain?
Phosphoryl choline moiety linked to ceramide
What is the deficient enzyme in Tay-Sachs disease?
B-Hexosaminidase A
What is the accumulating substrate in Tay-Sachs?
Ganglioside (Gm2)
Ganglioside is also known as what?
Gangliosidosis
What are the distinguishing features of Tay Sachs?
- Cherry-red spot on macula
- Onion-shell inclusions in lysosomes
- Normal Retina
- Progressive neurodegeneration after 3-6 months
- Blindness
- Developmental milestone delay
- Death by 2-6 yr/old
How can carriers of Tay Sachs be detected?
Enzyme assays
Hunter’s syndrome is genetically categorized as?
X-linked recessive
Which is the most common lysosomal storage disorder?
Gaucher disease
What is the deficient enzyme in Gaucher disease?
B-glucosidase
What is the accumulating substrate in Gaucher disease?
Glucosyl Ceramide
Glucosyl Ceramide is also known as what?
Glucocerebroside
What happens to macrophages in Guacher disease?
become engorged with glucocerebrosides
What describes the appearance of the cytoplasm of the Gaucher cells in Gaucher disease?
Crumpled tissue paper
Genetically, what sort of disorder is Fabry’s disease?
x-linked recessive
What is the deficient enzyme in Fabry’s disease?
alpha-Galactosidase
What substate accumulates in Fabry’s disease?
Globoside
What is another name for Globoside/
Ceramide trihexoside
How is Fabry disease manifested?
- Skin rash “bathing-trunk distribution”
- Peripheral neuropathy
What is the deficient enzyme in Niemann-Pick disease?
Sphingomyelinase
What is the substrate that accumulates in Niemann-Pick disease?
Sphingomyelin
What is spingomyelin?
A sphingophospholipid
In niemann-pick disease, where does sphingomyelin accumulate?
Neural tissues
What is the difference between Niemann Pick type A and type B?
Type A- severe infantile form = death by 2-3 yr/old
Type B: appears later in childhood; hepatosplenomegaly
In Niemann-Pick disease, cells containing sphingomyelin have a ________ appearance.
Foamy Cell
Which lysosomal storage diseases present with cherry-red spots on the macula?
Tay-Sachs
Niemann-Pick
What is the deficiency enzyme in Metachromatic Leukodystrophy?
Aryl Sulfatase A
What is the accumulating substrate in metachromatic leukodystrophy?
Sulfatide
In metachromatic leukodystrophy, sulfatide cannot be broken down into what?
Galactosyl Ceramide
In Fabry disease, Globoside cannot be broken down into what?
Lactosyl Ceramide
In Tay-Sachs disease, Ganglioside (Gm2) cannot be broken down into what?
Ganglioside (Gm3)
In Gaucher disease, Glucosyl ceremide cannot be broken down into what?
Ceramide
In Niemann-Pick disease, Sphingomyelin cannot be broken down into what?
Ceramide
In Pompe disease, a small amount of cellular glycogen is degraded by what enzyme?
Lysosomal acid maltase
Lysosomal acid maltase (Pompe disease) is also known as what?
1->4 glucosidase
What parts of the body do glycogen accumulate in Pompe disease?
Heart
Muscle
Kidney
Liver
What type of glycogen disorder is Pompe disease?
Glycogen storage disorder type II
In I-cell disease, what does the golgi fail to do?
Phosphorylate mannose to form mannose-6-phosphate
In I-cell disease, what accumulates in the lysosomes?
Glycosaminoglycans and sphingolipids
Why is it called I-cell disease?
Unique feature: fibroblasts contain intracytoplasmic inclusions.
Cells termed “inclusion cells”
