Phosphofructokinase Deficiency
Encyclopedia
Phosphofructokinase deficiency, also known as Glycogen storage disease type VII or Tarui's disease, is metabolic disorder with autosomal recessive inheritance.
It may affect humans as well as other mammal
s (especially dog
s). In humans it is the least common type of glycogen storage disease
.
) of the phosphofructokinase
enzyme
impairs the ability of cells such as erythrocytes and rhabdomyocyte
s to use carbohydrate
s (such as glucose
) for energy.
The mutation impairs the ability of phosphofructokinase to phosphorylate fructose-6-phosphate prior to its cleavage into glyceraldehyde-3-phosphate which enters the energy generation phase of glycolysis
, effectively limiting energy production.
Unlike most other glycogen storage diseases, it directly affects glycolysis
.
), myoglobinuria
, as well as with haemolytic anaemia causing dark urine a few hours later. Hyperuricemia
is common.
Phosphofructokinase deficiency also presents in a rare infantile form. The infantile form causes severe myopathy and leads to death in infancy or early childhood.
, phosphoglycerate mutase
, lactate dehydrogenase
, beta-enolase and aldolase A.
A diagnosis can be made through a muscle biopsy that shows excess glycogen and then further tests that will show the levels of phosphofructokinase enzyme.
It may affect humans as well as other mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s (especially dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s). In humans it is the least common type of glycogen storage disease
Glycogen storage disease
Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...
.
Pathophysiology
In this condition, a deficiency of the M subunit (PFKMPFKM
6-phosphofructokinase, muscle type is an enzyme that in humans is encoded by the PFKM gene.-Further reading:...
) of the phosphofructokinase
Phosphofructokinase
Phosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
impairs the ability of cells such as erythrocytes and rhabdomyocyte
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
s to use carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s (such as glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
) for energy.
The mutation impairs the ability of phosphofructokinase to phosphorylate fructose-6-phosphate prior to its cleavage into glyceraldehyde-3-phosphate which enters the energy generation phase of glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
, effectively limiting energy production.
Unlike most other glycogen storage diseases, it directly affects glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
.
Presentation
The disease presents with exercise-induced muscle cramps and weakness (sometimes rhabdomyolysisRhabdomyolysis
Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
), myoglobinuria
Myoglobinuria
Myoglobinuria is the presence of myoglobin in the urine, usually associated with rhabdomyolysis or muscle destruction. Myoglobin is present in muscle cells as a reserve of oxygen.-Causes:...
, as well as with haemolytic anaemia causing dark urine a few hours later. Hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
is common.
Phosphofructokinase deficiency also presents in a rare infantile form. The infantile form causes severe myopathy and leads to death in infancy or early childhood.
Diagnosis
Other deficiency diseases with similar signs and symptoms include deficiencies of phosphoglycerate kinasePhosphoglycerate kinase
Phosphoglycerate kinase is a transferase enzyme used in the seventh step of glycolysis. It transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-Phosphoglycerate....
, phosphoglycerate mutase
Phosphoglycerate mutase
-Overview:Phosphoglycerate mutase is an enzyme that catalyzes step 8 of glycolysis. It catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate to 2-phosphoglycerate through a 2,3-bisphosphoglycerate intermediate.This enzyme is...
, lactate dehydrogenase
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
, beta-enolase and aldolase A.
A diagnosis can be made through a muscle biopsy that shows excess glycogen and then further tests that will show the levels of phosphofructokinase enzyme.