heritable enzyme deficiencies of the carbohydrate metabolism Flashcards
how is the heritable enzyme deficiency usually inherited?
it is usually autosomal resessive and related to the X chromosome
usually homozygous recessive
passed on by heterogenous carriers
diagnosis of heritable enzyme deficiencies?
- diagnosis of certain reaction specific metabolites in the blood and urine
- measurement of enzyme activity (ELISA etc.)
- DNA testing - special test kits are available for frequent diseases
therapy for heritable enzyme deficiencies?
- no specific casual therapy for most of the diseases - only symptomatic therapy
- searching for carriers and excluding from breeding is the real solution
- Genetic therapy -
- Bone marrow transplantation - highly unsuccesful
- Enzyme replacement -systematic replacement of enzymes
Biochemical role of pyruvate kinase?
- one of the enzymes of glycolysis
the 4 subunits of isoenzymes?
- PK - M1 - striated and heart muscle
- PK - M2 - mostly Fetal tissues
- PK - L - Liver
- PK - R - RBCs
what happens if the genes of L and R isoenzymes are damaged?
metabolic disorder in the liver and RBCs
most common breeds to have a lack of pyruvate kinase enzyme?
Dogs:
- Westie
- Beagle
- Chiuahua
Cats:
- Abessinian
- Somali
consequences of lack of PK in the liver?
- Glycogen accumulation
- Hepatomegaly
- Decreased ATP production
- intensive B oxidation
consequences of lack of PK in RBCs?
- Lack of ATP - cell heavily damaged
- membrane not protected from free radicals - membrane is fragile - haemolysis - haemolytic anaemia
- irregular shaped cells - Burr cells
what can cause the formation of Burr cells?
lack of PK
symptoms for the lack of PK?
- Haemolytic anaemia
- Pale mucosal membranes
- Jaundice
therapy for PK deficiency?
- Symptomatic therapy - Splenectomy, transfucion etc.
- not always unfavorable prognosis - patients can live for years with proper treatment
what is Gierke - disease?
lacking the enzyme: glucose - 6 - phosphatase
(liver and kidneys)
consequences of the lack of glucose -6- phosphatase?
- accumulation of glucose -6- phosphate = allosteric activation of glycogen synthase = glycogen accumulation
- Inhibition of blood glucose production - Hypoglycaemia
symptoms of Gierke - disease?
- notably enlarged liver
- skeletal and heart muscle: degeration due to glycogen storage
- strong hypoglycaemic spasms in the case of starvation or intensive load
Gierke - disease therapy?
- symptomatic treatment
- Glucose I.V.
- Special diet - energy deficiency
- unfavourable prognosis in each
what is Pompe - disease?
lacking of enzyme
Lysosomal exo - amylo - 1.4 - glucosidase
glycogen accumulation and energy deficiency = muscle weaknes
symptoms of Pompe - disease?
- cardiomegaly form - large amount of glycogen accumulated in the heart muscle = fast death
- Neuromuscular form: glycogen accumulation in the brain - CNS symptoms
treatment for pompe - disease?
no known treatment
poor prognosis
what is Cori - forbes disease?
lacking of enzyme
amylo - 1.6 - glucosidase (debranching enzyme)
splitting the branches of glycogen during glycogenolysis
Cori forbes disease occurence?
- in akita and german shepherd breeds
pathogenesis and symptoms of cori - forbes disease?
- Muscle disease - weakness - 2 month old dog
- Hepatomegaly
- Hypoglycaemia - in case of starvation
- life span is not reduced significantly
types of cori forbes disease?
- Type I: enzyme deficiency in the liver and the muscles as well
- Type II: enzyme deficiency only in the liver
cori - forbes therapy?
symptomatic therapy - Glucose IV., hepatic protection
Prognosis: not definatley unfavourable
what is Andersen Disease?
lacking the enzyme:
Transglucosidase
where was Andersen disease first described?
in Norwegian forest cat
pathogenesis of Andersen disease?
formation of abnormal shaped, branchless, straight chained glycogen in the tissues
the immune system recognises it as foregin body material and attacks the storage tissues (liver, muscles and kidneys)
symptoms and therapy of andersen - disease?
- consequences of glycogen accumulation
- severe degradation in CNC and PNS, muscles, liver and heart
- Hepato and splenomegaly
- muscles - tremors , muscle atrophy, shrinking muscles
No specific treatment
properties of Tarui - disease?
Lacking of enzyme
Phosphofructokinase I
regulator of glycolysis
Tarui - disease occurence?
first described in english springer spaniels
8 months of age
cocker spaniels incidence of recessive allele is 10%
Diagnosis of Tarui - disease?
non invasive DNA test kits
tarui disease pathogenesis?
- Blocked glycolysis
- Glycogen accumulation
symptoms and therapy of tarui disease?
- RBC haemolysis - Haemolytic anaemia
- Muscle weakness, pain, and rigidity of muscles
- Hepatomegaly
Only symptomatic therapy
What is progressive retina atrophy?
lacking (damaged) enzyme
Phosphodiesterase type 6
enzyme responsible for central role in enabling light detection
where is progressive retina atrophy most common?
welsh corgies
symptoms of progressive retina atrophy?
- visual disturbances - worsen with time
- irreversible damage - ending with complete blindness
diagnosis of progressive retina atrophy?
- Fundus scopy
- Electroretinography
- Special DNA test
- Testing labradors is obligatory in Hungary
treatment of progressive retina atropy?
no effective treatment
potential for antioxidant treatment in the future!
