Inborn Errors of Metabolism Flashcards
1
Q
Sphingolipidoses
A
- Mutations in the genes encoding lysosomal hydrolases
- Defects in the degradation of sphingolipids are associated with progressive neurodegeneration since the nervous system is rich in these lipids
- autosomal recessive for all sphingolipidoses
- except for Fabry’s disease, which is an X-linked disorder
2
Q
Tay-Sachs disease deficiency
A
- Hexosaminidase A
- Prevalent in Ashkenazi descent
3
Q
Tay-Sachs disease symptoms
A
- mental impairment
- early mortality
- “cherry-red” spots in their eyes
4
Q
Fabry’s disease deficiency
A
- α-Galactosidase A
- A mutation in the gene causes build up to harmful levels of globoside or ceramide trihexoside in the eyes, kidneys, autonomic nervous system, and cardiovascular system
- Fabry disease is one of several lipid storage disorders and the only X-linked sphingolipidoses
5
Q
Fabry’s disease symptoms
A
- heart failure
- pain
- skin rashes
- often die prematurely of complications from strokes, heart disease, or renal failure
- Angiokeratomas: small, raised reddish blemishes on the skin (chest and back)
- Renal failure
6
Q
Tay-Sachs disease accumulating substance
A
- GM2 ganglioside
- Gangliosides are synthesized and degraded rapidly in early life as the brain develops
- Normal development for the first few months of life. Then, as nerve cells become distended with fatty material, a relentless deterioration of mental and physical abilities occurs
7
Q
Fabry’s disease accumulating substance
A
- globoside or ceramide trihexoside build up in the eyes, kidneys, autonomic nervous system, and cardiovascular system
8
Q
Metachromatic leukodystrophy deficiency
A
- arylsulfatase
9
Q
Metachromatic leukodystrophy accumulating substance
A
- sulfatide
10
Q
Metachromatic leukodystrophy symptoms
A
- mental impairment
- damage to protective sheaths surrounding nerve, kidneys, gallbladder, and other organs
- Loss of muscle control
- Feeding and swallowing difficulties
- Metachromatic granules
- 3 forms of the disease
▪ Late infantile: MLD symptoms begin by ages 1 - 2
▪ Juvenile: MLD symptoms between ages 4 and 12
▪ Adult and late-stage juvenile: symptoms may occur >14, or as late as the 40s or 50s
11
Q
Gaucher’s disease deficiency
A
- glucocerebrosidase
- prevalent in Ashkenazi descent
12
Q
Gaucher’s disease accumulating substance
A
- glucocerebroside deposition in
hematopoietic organs including the bone marrow, spleen and liver
13
Q
Gaucher’s disease symptoms
A
- mental impairment
- Loss of bone density and bone pain and fractures
- Cognitive and mental impairments
- Fatigue and lack of energy due to anemia
- Seizures
- Gaucher cells
- Showing “crinkled paper” cytoplasm and glycolipid-laden macrophage
14
Q
Niemann-Pick disease deficiency
A
- Sphingomyelinase
15
Q
Niemann-Pick disease accumulating substance
A
- Sphingomyelin LDL-derived cholesterol accumulating in the spleen, liver, lungs, bone marrow, and brain
- Fatal
16
Q
Niemann-Pick disease symptoms
A
- mental impairment
- early mortality
- Affected cells become enlarged
- Histology demonstrates lipid laden macrophages in the marrow
- “sea-blue histiocytes” on pathology
17
Q
The 4 major classes of glycosphingolipids
A
◼ Cerebrosides: contain 1 sugar, principally galactose (galactocerebrosides)
◼ Globosides: contain 2 or more sugars
◼ Gangliosides: contain 2 or more sugars plus sialic acid
◼ Sulfatides: sulfuric acid esters of
galactocerebrosides
18
Q
Tay-Sachs treatment
A
None
19
Q
Fabry’s disease treatment
A
- ERT has been approved by the FDA
* can reduce lipid storage, ease pain, and improve organ function
20
Q
Gaucher disease type 1
A
- most common
- involves bone disease, anemia, an enlarged spleen and thrombocytopenia
- affects both children and adults and is most common in the Ashkenazi Jewish population
21
Q
Gaucher disease type 2
A
- usually begins in infancy with
severe neurologic involvement - can lead to rapid, early death
22
Q
Gaucher disease type 3
A
- may cause liver, spleen, and brain problems
- Patients may live into adulthood
23
Q
Sandhoff disease deficiency
A
- hexosaminidase A and B
24
Q
Sandhoff disease accumulating substance
A
- globoside
25
Sandhoff disease symptoms
- similar to Tay-Sachs disease but occur more commonly in non-Jewish people of Argentina and Lebanon
26
GM1 Gangliosidosis deficiency
- beta-galactosidase
27
GM1 Gangliosidosis accumulating substance
- GM1 gangliosides
28
GM1 Gangliosidosis symptoms
- infantile form is named pseudo-Hurler disease b/c of rapid neurological deterioration, coarsened facial features and hepatosplenomegaly
- more common in the pop. of Malta
29
Krabbe disease deficiency
- beta-galactosidase
30
Krabbe disease accumulating substance
- galactocerebroside
31
Krabbe disease symptoms
- demyelination in the white matter of the brain and peripheral nerves
- globoid cells are characteristic
- presents w/ blindness, deafness, paralysis and mental retardation
32
Mucopolysaccharidoses (MPS) types
- MPS I – Hurler-Scheie syndrome
| - MPS II – Hunter disease
33
Mucopolysaccharidoses (MPS) characteristics
- Normal degradation of carbohydrate chains of glycosaminoglycans
- defective enzyme cause permanent, progressive cellular damage affecting appearance, physical abilities, mental development
- may range from normal intellect to
profound mental impairment
34
Mucopolysaccharidoses (MPS) accumulating substance
- glycosaminoglycans
35
Mucopolysaccharidoses (MPS) symptoms
- rough facial features
* thick lips, enlarged mouth and tongue
- dwarfism
- enlarged organs (liver or spleen)
36
Hurler-Scheie syndrome deficiency
- iduronidase
37
Hunter syndrome deficiency
- X-linked deficiency of enzyme iduronate sulfatase
38
Hurler-Scheie syndrome accumulating substance
- dermatan sulfate
| - heparan sulfate
39
Hurler-Scheie syndrome symptoms
- gargoyle-like faces
- mental retardation
- dwarfism
- ischemic heart disease
- corneal clouding
40
Hurler-Scheie syndrome treatment
- enzyme replacement
41
Hunter syndrome accumulating substance
- dermatan sulfate
| - heparan sulfate
42
Hunter syndrome symptoms
- similar to Hurler syndrome but less severe
| - no corneal clouding
43
Mucolipidoses (ML) general characteristics
- Autosomal recessive
- Accumulation of sphingolipids, and/or glycolipids in visceral and mesenchymal cells in neural tissue
- leads to swelling and damage of organs
- Dysostosis multiplex occur frequently
* deformity in the developmental stages of cartilage and bone
- Symptoms range from mild learning disabilities to severe mental impairment and skeletal deformities
- No cure
44
Mucolipidoses (ML) types
- Mucolipidosis II (inclusion-cell, or I-cell disease)
- Mucolipidosis III (pseudo-Hurler
polydystrophy)
45
Mucolipidoses (ML) deficiency
- N-acetylglucosamine-1-phosphotransferase
* phosphorylates target carbohydrate residues on N-linked glycoproteins
* Without this phosphorylation, the glycoproteins are not destined for lysosomes, and they escape outside the cell
46
Mucolipidoses (ML) symptoms
- skeletal abnormalities
- vision problems
- developmental delays
