Lysosomal Storage Disease Flashcards
What are the disease that can be caused by changes with sphingolipids?
Fabry’s disease (deficiency of alfa-galactosidase A)
Gaucher’s disease (deficiency of glucocerebrosidade)
Niemann Pick disease (deficiency of acid sphingomyelinase)
Krabbe’s disease (deficiency galactocerebrosidase)
Tay-Sachs disease (deficiency of hexosaminidase A)
Metachromatic Leukodystrophy (deficiency of arylsulfatase A)
What are the diseases that can be caused by changes in glycosaminoglycans?
Hurler’s syndrome (dificiency of a alfa-L-iduronidase)
Hurter’s syndrome (deficiency of iduronate 2-sulfatase)
What is the disease that can be caused by alfa galactosidase A deficiency?
Fabri’s disease
What is the disease that can be caused by glucocerebrosidase deficiency?
Gaucher’s disease
What is the disease that can be caused by acid sphingomyelinase deficiency?
Niemann-Pick disease
What is the disease that can be caused by galactocerebrosidase deficiency?
Krabber’s disease
What is the disease that can be caused by hexosaminidase A deficiency?
Tay-Sachs disease
What is the disease that can be caused by arylsulfatase A deficiency?
Metachromatic leukodystrophy
What is the disease that can be caused by alfa-L-iduronidase deficiency?
Hurler’s syndrome
What is the disease that can be caused by iduronate 2-sulfatase deficiency?
Hunter’s syndrome
What are the classic symptoms that can be seen in Fabry’s disease?
Child with pain in hands/feet
Lack of sweat
Skin findings
Acummulation of ceramide trihexoside!!!
What are the classic symptoms that can be seen in Gaucher’s disease?
Child of Ashkenazi Jewish descent
Splenomegaly on exam
Anemia
Bruising (low plaquets)
Joint pain/fractures
Accumulation of glucocerebroside!!
What are the classic symptoms that can be seen in Niemann-Pick disease?
Previously well, healthy child
Weakness, loss of motor skills
Enlarged liver or spleen on physical exam
Cherry red spot
Accumulation of sphingomyelin!!!
What are the classic symptoms that can be seen in Krabbe’s disease?
Only neuro symptoms -> progressive weakness, development delay, floppy limbs, loss of head control, absent reflexes, optic atrophy, often fever without infection, usually death < 2 yrs
Globoid cell leukodystrophy
What are the classic symptoms that can be seen in Tay-Sachs disease?
3-6 months old infant
Ashkenazi Jewish descendent
Development delay
Exaggerated startle response
Cherry red spot
NO hepatosplenomegaly
Lysosomes with onion skinning
Accumulation of GM2 ganglioside
What are the classic symptoms that can be sem in Metachromatic leukodystrophy disease?
~ 2 years old (Krabbe’s disease <6 months)
Ataxia
Hypotonia
Dementia can develop
Accumulation of sulfatides!!
What are the classic symptoms that can be sem in Hurler’s disease?
Facial abnormalites (coarse features)
Short stature
Intellectual disability
Hepatosplenomegaly
Dysostosis Multiplex
Corneal clouding
Ear, sinus, pulmonary infections (thick secretions)
Airway obstruction and sleep apneia (tracheal cartilage abnormalities)
Accumulation of heparan and dermatan sulfate
Symptoms 1st year of life.
What are the classic symptoms that can be sem in Hunter’s syndrome?
Later onset (1-2 years)
No corneal clouding
Behavioral problems
Learning difficult
Trouble sitting still
Often agressive behavior
Explain what is the cause of I Cell Disease?
Subtype of mucolipidosis disorders
Accumulation of both: sphingolipid and mucopolysaccharide
What are the symptoms that can be seen in I Cell Disease?
Similiar Hurler’s
Growth failure
Coarse facial features
Hypotonia/motor delay
Clouded corneas
Joint abnormalities
Dysostosis multiple
Frequent respiratory infections
What is the importance of mannose-6-phosphate (M6P)?
This is processing in Golgi apparatus. Added to lysosome proteins and directs enzymes to lysosome.
What is the disease that can be seen in failure of processing in the Golgi of M6P?
I Cell Disease
What are the key findings in I Cell Disease?
Deficient intracellular enzyme levels
Increased extracellular enzyme levels
Multiple enzymes abnormal
Intracellular inclusions in lymphocytes and fibroblasts.
What is the problem that can be seen in Pompe’s Disease?
Accumulation of glycogen in lysosomes due acid alpha glucosidase deficiency.
