Exam 4 Flashcards
Glycogen storage diseases
(GSDs)
Autosomal recessive disorders
Type 0 - VII + XI
- abnormally inherited glycogen metabolism in the liver or muscle
- build up of glycogen in tissues
Von Gierke
Type I GSD
- Deficiency of Glucose-6-Phosphatase (G6Pase) (1a) or G6P transporter (1b)
- Liver cannot release free glucose in hypoglycemia
- Excess G6P funneled back into glycolysis
- elevated lactate levels
- excess glycogen formation
- Doll-like appearance
Results In:
- Enlarged Liver + Kidney due to back up of G6P
- growth failure
- Severe fasting hypoglycemia + lactic acidemia
- hyperuricemia + hyperlipidemia
Key Feature to Remember:
Growth failure
Pompe
Type II GSD
worst of GSD
- Deficiency of lysosomal α-glucosidase (acid maltase)
- Infants have enlarged heart, liver, and tongue
- heart has high E demand t.f. expansion of mito # to compensate = enlarged heart
- adults have enlarged skeletal muscle
- no neurological effect
Results in
- Muscle hypotonia
- cardiac failure + cardiomegaly
- massive glycogen deposits in lysosomes
Treated with ERT
Cori
Type III GSD
short branched molecules
- Deficiency of debranching enzyme
- Hypertrophic cardiomyopathy during childhood
- Liver transaminases in GSD III are highest
Results In:
- Fasting hypoglycemia
- hepatomegaly
- Hypertrophic cardiomyopathy
- Glycogen has short branches
no treatment
Andersen Disease
GSD IV
long glycogen molecules due to synthesis defect
- Defect in Branching Enzyme
Results In:
- Hepatomegaly, hypertonia, muscle atrophy
- Glycogen Deposits abnormally long
- straight glucose polymers with little branching
- Progressive liver cirrhosis
McArdle
GSD Type V
- Defect Muscle Phosphorylase
- no liver affect
Results in
- Exercise-induced muscle pain, cramps, progressive weakness,
- myoglobinuria
- reduced lactate output
Hers
Type VI GSD
Most common
- Deficiency of liver phosphorylase
- Relies on Gluconeogenesis
- mild symptoms
Results in
- early childhood hepatomegaly + growth retardation
- Hypoglycemia
No treatment
Tarui Syndrome
Type VII GSD
- defect in PFK-1
- affects glycolysis
- inability to break glycogen
results in
- hemolytic anemia
- Exercise-induced muscle pain, cramps, progressive weakness
- myoglobinuria
- kidney failure
Franconi-Bickel Syndrome
Type XI GSD
- defect in GLUT2 transporter
- severe hepatomegaly
Results in
- glycogen accumulation in liver + kidney
- rickets
- growth retardation
- glucosuria
General treatments for GSD’s
- Frequent feeding
- Cornstarch
- during long periods of fasting
- High protein diet
- provides amino acids for gluconeogenesis
Lysosomal Storage Diseases
mostly monogenic autosomal recessive LSDs
2 X-lined LSDs
Defects in degradative enzymes leads to accumulation of macromolecules in lysosomes
significant impact on CNS
Enzyme replacement therapy
Treats symptoms but not underlying disease
Possible treatment when a patient has an enzyme deficiency
Fabry disease
X-linked
Deficiency in alpha-galactosidase A
involved in globoside degradation
accumulation of globoside
- red-purple skin rash
- kidney + heart failure
- burning pain in Lower EXTR
Treat using ERT – Fabrazyme (recombinant human alpha-galactosidase A)
Tay-Sachs disease
Deficiency in hexosaminidase A
involved in ganglioside degradation
accumulation of gangliosides (GM2)
- upper and lower motor neuron deficits
- visual difficulties
- cherry red macula
- increasing cognitive dysfunction
- seizures
common in ashkenazi jews
death by age 5
no treatment
Sandhoff disease
Deficiency in both hexosaminidase A (αβ) & hexosaminidase B (β2) due to defect in β subunit
involved in globoside degradation
accumulation of globosides + gangliosides (GM2)
- accelerated Tays-Sachs s/s
common in ashkenazi jews
death by age 3
no treatment
Niemann-Pick Disease
Type A + Type B
Deficiency in sphingomyelinase
accumulation of sphingomyelin in brain, spleen + liver
- Enlarged liver + spleen (lipid-filled)
- cognitive impairment
- cherry red macula
- early childhood death in Type A
