Glycogen storage diseases Flashcards
What are glycogen storage disease?
inherited disorders that affect glycogen metabolism
What areas in the body affected by glycogen storage disease?
liver and skeletal muscle
What do the disorders that affect the liver result in?
Hepatomegaly - enlarged liver
Hypoglycaemia - low blood sugar levels
What do the disorders that affect the muscle cause?
muscle cramps and weakness
What can glycogen storage disease also cause disturbances on?
Renal and CV
What is type 1 glyocogen disease?
Glucose-6-phosphatase defiency, von gierkes diseases
What does glucose-6-phosphatase do?
Catalyses the release of phosphate group allows free glucose to be released from the liver into the bloodstream
What does a defiency in glucose-6-phosphatase result in?
Large increase in intra-cellular G-6-P
What does type 1 defiency cause?
large accumulation of glycogen in the liver and kidney and inability to increase blood sugar levels in response to glucagon and adrenaline release
What are symptons of von gierkes disease?
Severe hepatomegaly and severe hypoglycaemia
What are the treatments for von gierkes disease?
treat hypoglycaemia of drug induced inhibition and continous intra-gastric feeding overnight
liver transplant
What is the surgical option for von gierkes disease?
surgical transposition of the portal vein - portal vein delivers glucose rich blood from the intestines to the liver - diverts glucose to peripheral tissues first
What is type 2 disease?
Pompes disease a-1,4 glucosidase defiency
What happens with type 2 disease?
most severe - die of cardio-resp failure before 1yr
What is enzyme a-1,4 glucosidase in involved in ?
gylcogen degradation in lysosomes - glycogen granules taken up by lysosomes and broken down
What does type 2 causes?
Accumulation of glycogen in lysosomes of all cells - disrupts lysosomal functions
how can type 2 disease detected by?
blood tests for mutations 1/85 people carry recessive trait
What does mutations cause?
destroy protein - infant onset pompes disease
mutations that leave enzyme intact adult/juve disease
What is treatment for type 2 disease?
without a-1-4 glucosidase glycogen builds up inside lysosome and ruptures damaging muscle tissue
GAA or enzyme replacement therapy
what is type 3 disease?
Coris disease - amylo1,6,glucosidase, debranching enzyme
What happens in type 3 disease?
Glycogen formed has abnormal structure and buils up - short outer chain accumulates in liver and muscle
What happens in type 3?
Absence of debranching enzyme - gylcogen cant be completely degraded, symptons appear in puberty
What are symptons of type 3 coris disease?
muscle weakness and liver problems, similiar to type 1 - not as sever hypoglycaemia
How do treat type 3 disease?
frequent feeding and high protein diet
What is type IV - 4 andersons disease?
deficiency of glycogen branching enzyme, amylo-transglycosylase
What does type IV do?
adds new branches in glycogen molecule during synthesis - results in reduced ability to store glucose residues as glycogen
What is severity of type IV 4?
one of most sever - rarely survive past age 4 - long unbranched chains make it very insoluve
What is main sympton of andersons disease?
liver dysfunction - immune response to abnormal glycogen
What is type V - 5 mcardles disease?
Muscle phosphorylase defiency
What happens in type V - 5?
glucose residues are removed from glycogen as G1-P by glycogen phosphorylase
What is affected in type 5?
glycogen breakdown in muscle affected leads to lack of glucose for glycolysis to produce ATP
What are symptons of type 5?
painful muscle cramps after exertion - muscle cant convert glycogen to glucose to lactate - muscle tissue breaksdown due to lack lactate
What is treatment of type V -5 ?
disease not fatal, quite harmless as long as strenuous exercise is avoided
What is type VI - 6 disease?
Liver phosphorlase defiency - Her’s disease
What happens in VI - 6 disease?
similiar to type 1, lack of glycogen phosphorylase in the liver - mild symptons
What are symptons of hers type 6 disease?
enlarged liver with mild hypoglycaemia - mild ketosis and retarded growth
Why does hypoglycaemia results from and ketosis?
Hypoglycaemia - inability to breakdown liver glycogen to increase blood glucose levels
Ketosis - non functioning TCA cycle
What is type VII disease? 7
muscle phosphofructokinase defiency taruis disease
What happens in type 7 disease?
defiency of phosphofuctokinase in muscle disrupts glycolysis - leads to build up of glucose-6,fructose,6 phosphate
What happens in type 7 disease?
high conc of glucose -6-phosphate increases the activity of glycogen synthase and UDP-glucose pyrophosphorylase
What does type 7 cause?
Build up of glycogen in the muscle - painful muscle cramps
What is type VIII - 8 ?
X-linked phosphorylase kinase defiency
What happens in type 8 disease?
defective phosphorylase kinase cant add phosphate to convert glycogen to phos b to active phos a
Why is glycogen not broken down?
lack of phosphorylated active form of glycogen phosphorylase - similiar symptons to type 6, this is x-linked
What is type XI? 9 ?
phosphorylase kinase defiency
What does type 9 disease cause?
autosomal recessive disease - from mutations in genes that encode phosphorylase kinase subunits
What is symptons of type 9?
different tisses have different isoenzymes of phosphorylase kinase - depends on affected organ
What is type 0 disease?
Liver glycogen synthase defiency
What does type 0 disease cause?
only glycogen with too little glycogen - glycogen synthase activity is low and suffer from hypoglycaemia after meals
