Lysosomal Storage Diseases Flashcards
Lysosomal Storage Diseases description?
Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation of abnormal metabolic products
What are 6 the sphingolipidoses?
1) Fabry Disease 2) Gaucher Disease 3) Niemann-Pick Disease 4) Tay Sachs Disease 5) Krabbe Disease 6) Metachromatic leukodystrophy
What enzyme is deficient in Fabry disease?
alpha-galatosidase A
What is the accumulated substrate in Fabry disease?
Ceramide trihexoside
What are the findings in Fabry disease?
Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease. Red macules or papules on abdomen or scrotum
What is the inheritance of Fabry disease?
X-linked Recessive
What enzyme is deficient in Gaucher Disease?
Glucocerebrosidase (beta-glucosidase)
What is the accumulated substrate in Gaucher Disease?
Glucocerebroside
Which is the most common lysosomal storage disease?
Gaucher
What are the findings in Gaucher Disease?
Hepatosplenomegaly, pancytopenia, aseptic necrosis of femur, bone crises, Gaucher cells
What are Gaucher cells?
lipid-laden macrophages resembling crumpled tissue paper
What is the treatment of Gaucher disease?
recombinant glucocerebrosidase
What is the inheritance of Gaucher disease?
Autosomal Recessive
What enzyme is deficient in Niemann-Pick Disease?
Sphingomelinase
What substrate is accumulated in Niemann-Pick Disease?
Sphingomyelin
What are the findings in Niemann-Pick Disease?
Progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells (lipid-laden macrophages)
What is the inheritance of Niemann-Pick Disease?
Autosomal Recessive
What enzyme is deficient in Tay-Sachs disease?
Hexosaminidase A
What is the accumulated susbstrate in Tay-Sachs?
GM2 ganglioside
What are the findings in Tay-Sachs?
Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly
What clinical symptom differentiates Niemann-Pick from Tay-Sachs?
Hepatosplenomegaly is present in Niemann-Pick but NOT Tay-Sachs
What enzyme is deficient in Krabbe disease?
Galatocerebrosidase
What is the accumulated substrate in Krabbe disease?
Galactocerebroside, psychosine
What are the clinical findings in Krabbe disease?
peripheral neuropathy, developmental delay, optic atrophy, globoid cells
What is the inheritance of Krabbe Disease?
Autosomal Recessive
What enzyme is deficient in Metachromatic Leukodystrophy?
Arylsulfatase A
What is the accumulated substrate in Metachromatic Leukoystrophy?
Cerebroside sulfate
What are the clinical findings in metachromatic leukodystrophy?
Central and peripheral demyelination with ataxia, dementia
What is the inheritance of Metachromatic leukodystrophy?
Autosomal Recessive
What are the (2) Mucopolysaccharidoses?
Hurler syndrome & Hunter Syndrome
What enzyme is deficient Hurler Syndrome?
alpha-L-iduronidase
What is the accumulated substrate in Hurler Syndrome?
Heparan Sulfate, Dermatan Sulfate
What are the clinical findings in Hurler Syndrome?
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
What enzyme is deficient in Hunter Syndrome?
Iduronate sulfatase
What are the accumulated substrates in Hurler syndrome?
Heparan sulfate, dermatan sulfate
What are the clinical findings in Hunter Syndrome?
Mild Hurler + aggresive behavior; no corneal clouding
What is the inheritance of Hurler Syndrome?
Autosomal Recessive
What is the inheritance of Hunter Syndrome?
X-linked Recessive
Mneumonic for this shit
NO MAN PICKS (NIEMANN-PICK) his nose with his SPHINGer (SPHINGOMYELINASE).
tay-saX lacks heXosamindase
HUNTERS see clearly (no corneal clouding) and aggressively aim for the X (X-linked).
Which lysosomal storage diseases have increased incidence in Ashkenazi Jews?
Tay-Sachs, Niemann-Pick, and some forms of Gaucher
