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GSD and LSDLouis CarrilloOsler Friday Pediatrics
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Objectives
To discuss Glycogen storage diseases presentation, deficiency,
diagnosis and treatment
To discuss Lysosomal Storage diseases presentation,
deficiency, diagnosis and treatment
Cardiac pathology associated with diseases
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LSDs
Valve dysfunction secondary to deposition of
glycosaminoglycans
Myocardial ischemia due to circumferential coronary arterial
narrowing through the entire vessel
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Hurler Disease
Deficieny in
Alpha L Iduronidase
Presents with:
Developmental delay
Gargoylism
Corneal Clouding
Hepatosplenomegaly
Cardiomyopathy from endocardial
fibroelastosis, may be seen with MR Can present in infants unlike other
Buildup of
Heparan Sulfate, dermatan sulfate
ERT
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Hunter Disease
Deficieny in
Iduronate sulfatase
Presents with:
Aggression
NO Corneal Clouding
Buildup of
Heparan sulfate and dermatan sulfate
ERT
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Fabry Disease
Deficieny in
Alpha galactosidase A
Presents with:
Angiokeratomas
Peripheral Neuropathy
LV hypertrophy; one variant limited to only heart
Buildup of
Ceramide trihexoside
Normal lifespan if treated correctly with ERT
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Krabbe Disease
Deficieny in
Galactocerebrosidase
Presents with:
Peripheral Neuropathy
Developmental Delay
Optic Atrophy
Globoid Cells which are?
Multinucleated macrophages
Buildup of Galactocerebroside
Dead baby by 2 years oldno treatment
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Gaucher Disease
Deficiency in:
Glucocerebrosidase(Beta Glucosidase)
MOST COMMON
Presents with:
Hepatosplenomegaly
Pancytopenia
Aseptic Necrosis of Femus
Buildup of
Glucocerebroside
Normal lifespan if treated correctly with ERT
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Niemann Pick Disease
Deficieny in
Sphingomyelinase
Presents with:
Hepatosplenomegaly
Neurodegeneration
Cherry Red Spot on macula
Foam Cellswhich are
Lipid Laden Macrophages
Buildup of Sphingomyelin
No treatment and dead by 2 years old but can survive to teens
depending on seveity of disease
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Tay-Sachs Disease
Deficieny in
Hexosaminidase A
Presents with:
NO Hepatosplenomegaly
Neurodegeneration
Developmental Delay
Cherry Red Spot on macula
Lysosomes with onion skin
Buildup of GM2 Ganglioside
No treatment and dead by 4
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Metachromatic
Leukodystrophy Deficieny in
Arylsulfatase A
Presents with:
Ataxia
Dementia
Peripheral and Central Demyelination
Buildup of
Cerebroside sulfate
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GSDs
15 different types
All Autosomal Recessive!! Except for which ones?? Fabry Disease
Hunter Disease
X-Linked Vacuolar Cardiomyopathy and Myopathy (Danon Disease) No longer classified as a glycogen storage because intracellular glycogen is
not always increased.
X-linked dominant defect in lysosome-associated membrane protein-2(LAMP-2) gene.
Skeletal myopathy, cardiomyopathy, conduction defects, and mentalretardation.
Males in childhood/adolescence
Females may not present until adolescence or adulthood.
Ventricular preexcitation and cardiomyopathy usually hypertrophic in malesand dilated in females.
Clusters of vacuolated myocytes suggestive of impaired autophagy.
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Pompe Disease (Type II)
Deficieny in
Lysosomal alpha 1,4 glucosidase (Acid Maltase)
Presents with:
Cardiomyopathy
Hypotonia
Increased CK and diagn
Diagnosis
Muscle Biopsy
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EKG in Pompe
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Echo in Pomp
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Cori Disease
Deficieny in
Alpha 1,6 glucosidase
Presents with:
Mild form of Type I
Normal Lactate
Normal gluconeogenesis
Treatment is High protein diet to stimulate gluconeogenesis
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McArdle Disease
Deficieny in
Skeletal muscle glycogen
phosphorylase (myophosphorylase)
Presents with:
Elevated Muscle Glycogen
Painful Muscle Cramps
MyoglobinuriaRED Urine
Arrhythmia from electrolyte abnormalities
Renal Fail/Rhabdo with extreme exercise Diagnosis:
Muscle biopsy
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Enzyme replacement therapy
Especially useful in Gaucher, Fabry, Hunter and GSD type II,
who can lead relatively normal lives with normal lifespans if
adherent to therapy
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