lysosomal storage diseases Flashcards
1
Q
NP
- Mutationsin the NPC1 or NP2 gene
- Causes impaired cellular trafficking and homeostasis of cholesterol ; buildup of unesterified cholesterol in lysosomes
- Clinical presentation is heterogeneous with regard to age of onset and type and severity of neurologic and psychiatric symptoms, as well as visceral involvement
Prognosis is poor, with most patients dying before the age of 25 years
A
type C NP
2
Q
- Characterized by accumulation of sphingomyelin in cellular lysosomes in the liver, spleen, and lungs
- Deficiency in the enzyme acid sphingomyelinase (ASM)
- Associated with foam cells and sea-blue histiocytes in the bone marrow
A
niemann-pick’s disease
3
Q
lipid storage disease
- deficient enzyme: hexosaminidase B
- accumulated substance: globosides
A
sandhoff’s disease
4
Q
lipid storage disease
- deficient enzyme: beta-galactosidase
- accumulated substance: galactocerebroside
A
krabbe’s disease
5
Q
MPS
- enzyme deficiency: a-l-iduronidase
- clinical features: coarse facies, short stature, corneal clouding, joint stiffening, umbilical hernia, dysostosis multiplex, hepatosplenomegaly, frequent upper respiratory infections, cognitive impairment; death before 10 years old
A
hurler syndrome
6
Q
lipid storage disease
- deficient enzyme: hexosaminidase A
- accumulated substance: GM2-gangliosides
A
- tay-sach’s disease
- sandhoff’s disease
7
Q
- Are qualitative disorders involving monocytes and macrophages
- The macrophages are particularly prone to accumulate undegraded lipid products, which subsequently leads to an expansion of the reticuloendothelial tissue
EXAMPLES:
* GAUCHER’SDISEASE
* NIEMANN-PICK’S DISEASE
A
lipid storage diseases/sphingolipidoses
8
Q
MPS
- enzyme deficiency: a-l-iduronidase
- clinical features: hepatomegaly, joint contractures, cardiac valve abnormalities, corneal clouding; prolonged survival but with disability
A
scheie syndrome
9
Q
MPS
- enzyme deficiency: heparan N-sulfatase
- clinical features: hirsutism, coarse facial features, behavioral problems, aggressive behavior, speech delay, hepatomegaly; most die before 20 years old
A
sanfilippo syndrome
10
Q
MPS
- enzyme deficiency: heparan acetyl-coa: a-glucosaminidase, N-acetyltransferase
- clinical features: delayed psychomotor development, behavioral problems, sleeping/hearing problems, coarse facial features, recurrent infection, diarrhea, epilepsy, and retinitis pigmentosa
A
sanfilippo syndrome
11
Q
- Are a family of inherited disorders of mucopolysaccharide or glycoaminoglycan (GAG) degradation
- Each MPS is caused by deficient activity of an enzyme necessary for the degradation of dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate
- The partially degraded material builds up in lysosomes and results in serious physical and cognitive problems and shortened survival
- Presence of Alder-Reilly bodies in neutrophils, monocytes, and lymphocytes ; macrophages in the bone marrow canalso demonstrate cytoplasmic metachromatic material
A
mucoplysaccharidoses
12
Q
lipid storage disease
- deficient enzyme: arylsulfatase A
- accumulated substance: sulfatide
A
metachromatic leukodystrophy
13
Q
lipid storage disease
- deficient enzyme: alpha-galactosidase
- accumulated substance: ceramide trihexoside
A
fabry’s disease
14
Q
lipid storage disease
- deficient enzyme: ceramidase
- accumulated substance: ceramides
A
farber’s disease
15
Q
NP
- Non-neuronopathicform ; more common in individualsof Northern African descent
- 10-20%normalenzyme activity ; mutation in the SMPD1 gene
- Presents in the first decade to adulthood with a variable clinical course
- Although there is no neurocognitive impairment, patients experience massive hepatosplenomegaly, heart disease, and pulmonary insufficiency
A
type B NP
16
Q
NP
- Acuteneuronopathic form ; affects mostly Eastern European Jews
- <5%normalsphingomyelinase activity ; mutation in the SMPD1 gene
- Present in infancy and is associated with failure to thrive, lymphadenopathy, hepatosplenomegaly, vision problems, and rapid neurodegenerative decline that results in death, usually by 4 years of age
A
type A NP
17
Q
- Are a group of more than 50 inherited enzyme deficiencies resulting from mutations in genes that code for the production of lysosomal enzymes
- The result is flawed degradation of phagocytized material and buildup of undigested substrates within lysosomes
- This causes cell dysfunction, cell death, and a range of clinical symptoms; all cells containing lysosomes can be affected
- areclassified according to the underdegraded macromolecule that accumulates in the cell
A
lysosomal storage diseases
18
Q
- Mostcommonofthelysosomal lipid storage diseases ; at least 1 in 17 Ashkenazi Jews are carriers
- It is an autosomal recessive disorder caused by a defect or deficiency in the catabolic enzyme beta-glucocerebrosidase
- Accumulation in sphingolipid glucocerebroside in macrophages throughout the body, including osteoclasts in bone and microglia in the brain
- Bone marrow replacement contribute to anemia and thrombocytopenia
A
gaucher’s disease
19
Q
can be found in bone marrow of some patients with thalassemia, chronic myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, and plasma cell neoplasms
A
pseudo-gaucher cells
20
Q
lipid storage disease
- deficient enzyme: GM1-Beta-Galactosidase
- accumulated substance: GM1-gangliosides
A
GM1-gangliosidosis
21
Q
MPS
- enzyme deficiency: iduronate sulfatase
- clinical features: coarse facial features, short stature, skeletal deformities, joint stiffness, mental retardation
A
hunter syndrome
22
Q
MPS
- enzyme deficiency: galactose-6-sulfatase, B-galactosidase
- clinical features: musculoskeletal abnormalities, short stature, pulmonary and cardiac dysnfunction, hearing loss corneal clouding; most die before 30 years old
A
morquio syndrome
23
Q
MPS
- enzyme deficiency: a-N-acetylglucosaminidase
- clinical features: cardiomegaly, coarse facial features, progressive dementia, convulsions, survive into 20s, 30s
A
sanfilippo syndrome
