Description

Gangliosidose is a so called lysosomal storage disease, a so called enzymopathy (= a defect in the production of a necessary enzyme).

To understand, what a lysosomal storage disease is, we must have a look at an animal cell and will try to figure out, what 'lysosomal' and 'gangliosidose' and 'storage' mean.
So, we need some knowledge about molecular-biology and biochemistry.

	Click on the part of the cell having a number or on the number itself to read more.
Structure of an animal cell The little organs within the cell are called organelles.

The lysosomal enzymes are to be found in a little organelle within the cell called Lysosom. Lysosomal enzymes break down macromolecules (large molecules) and other materials that have been taken up by the cell during the process of endocytosis.
Endocytosis is the process, where macromolecules and particles from outside the cell are taken up by the cell via a progressive invagination (inpouching) by forming a membrane-bound vesicle (=bubble) within the cytoplasm of the cell. The vesicle then fuses with the lysosom and the lysosomal enzymes carry out their appointed task of destruction (by hydrolysis) without normally damaging the cell itself.

What are enzymes?

Enzymes are involved in every process in an organism, processes like to see, to hear, like the blood pressure, like breathing, like digestion, how the nerves transmit information, how the brain works, etc., are based on highly complex electro-chemical processes.
Each little cell needs also processes for its survival, i.e. a cell needs to breath, needs to digest, needs a certain pressure, needs to regenerate itself, and so on. Thus, those bio-chemical processes take place in every cell with the help of enzymes.

Enzymes are named:
<the substance on which they work or the work they do> + 'ase'.
Enzymes are internationally classified into 6 groups after the effect they have:

• Oxidoreductases
• Transferases
• Hydrolases (EC 3):
  splitting chemical connections by using water (Greek: hydros).
  • Some sub-groups are: Amylases, Glycosidases (EC 3.2.1), Peptidases, Esterases

    Beta-Galactosidase (EC 3.2.1.23), a sub-group of Glycosidases:
    an enzyme that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides.
    See also: National Library of Medicine.
    For those who are interested, you may also look at BRENDA, and look here  under "Diseases", you will find GM1 and GM2 Gangliosidose here.
    β-L-N-acetylhexosaminidase (EC 3.2.1.52), also a sub-group of Glycosidases:
    Those are enzymes that catalyze the hydrolysis of N-acylhexosamine residues in N-acylhexosamides. Hexosaminidases also act on Glucosides; Galactosides; and several Oligosaccharides.
    See also: National Library of Medicine.
    For those who are interested, you may also look at BRENDA, and look here  under "Diseases", you will find GM2 Gangliosidose here.

• Synthases, also called Lyases
• Isomerases
• Synthetases or Ligases

Above there are underlined some enzymes having also a hyperlink, those enzymes are involved in Gangliosidose in cats. Those are the enzymes working in the Lysosomes (besides another 50 enzymes).

But before we can conclude our excurse into biology and biochemistry we need to know what are Gangliosids and how those enzymes underlined above are involved.

What is a Gangliosid?

Gangliosids are Glycolipids (glycos = sugar, lipid = fat) which are located in the cell membrane and anchored there via their Lipid-part - remember the picture about the cell membrane. Compared to Cerebrosids those Glycolipids are complex chemical structures having up to seven glycose residues. Those glycose residues which are on the outer side of the cell membrane are involved via their negative polarized Sialin-acid how the surface of the cell membrane looks like and permanently changes its surface.
The highest concentration of Gangliosids can be found in the central nervous system, and here in the grey matter (grey substance, substantia grisea) of the brain with 6% of all Lipids. In the nervous system there are stored many different types of Gangliosids, whose consistency may change during the development or due to different environments (for example different temperatures). Gangliosids are involved in the transmission and storage of information by the neurons (=nervous cells), but they are also important in tumor markers (a higher concentration of Gangliosids in many cancer diseases may give an information about the progression of tumors).

And exactly in the destruction (=splitting into its parts) of the Gangliosids there are involved those above mentioned enzymes in the Lysosomes.
If the destruction of Gangliosids by those Glykosylhydrolasen (see the Glycosidases underlined above) is disturbed, that may result in very severe diseases.
That means, if the amount of Gangliosids stored in the neurons is too high, i.e. the Gangsliosids cannot be destructed, than it is called a "storage disease". And because the destruction of Gangliosids is done by the Lysosomes with the help of very specific enzymes, the storage disease is called a lysosomal storage disease.

The Gangliosids are named like this:
G + A (=asalio= without Sialin-acid)
G + M (=monosalio = with one Sialin-acid)
G + D (=disalio = with two Sialin-acids)
and so on.
And then they are further classified according to the length of the Glycose-part with a number like this:
GM₁
GM₂
GM₃
etc.

What are the commonly known storage diseases?

In general:
The disease is named by suffixing '-ose'.
The table below lists the diseases in humans, but those are similar in cats and dogs.

Which types of GM-Gangliosidoses may cats have?

Which symptoms do cats develop?

Cats affected with GM1- or GM2-Gangliosidose show progressive neurological dysfunction, head tremors, co-ordination problems and tremors in hind legs, premature thymic involution, stunted growth, and finally premature death.
GM1-Gangliosidose signs become obvious at an age of 4-6 months and progresses slower than GM2 up to 12-14 months.
GM2-Gangliosidose signs become obvious earlier at an age of 3-4 months and progresses faster than GM1-Gangliosidose.

Please note:
All GM-Gangliosidoses lead to premature death.

Inheritance of GM-Gangliosidose in cats

In both GM1- and GM2-Gangliosidose inheritance is autosomal recessive.
Autosomal means that the disease is inherited independently from the sex.
Recessive means that a cat must have both genes of the gene-pair to show clinical signs. If a cat has only one gene of the pair, the cat itself remains healthy and does not show any signs.
And that makes those diseases so dangerous. Just make the following calculation: If 1% of the cats in those breeds is affected it gives 18% who carry the disease.
And also think about that very seriously that Tom-cats do spread the disease much faster than queens, because they can sire more queens faster than queens can give birth to kittens.

Cat Breeds, likely to inherit GM-Gangliosidose

• Korat
• Siamese
• European Shorthair
• Domestic cat
• Burmese

Test method in cats

There is a DNA-Test available.
The test is a blood test, there is needed 1cc (about 1ml) of so called EDTA-blood (EDTA = ethylene-diamine-tetra-acetic acid). EDTA is a chelating agent and anticoagulant added to the blood sample, such as Heparin.
From that blood the DNA is isolated, and those parts, where the defect genes are located are multiplied in millions with the so called Polymerase Chain Reaction (PCR). A genetic analyzer reads those parts and makes them visible.

Consequences for breeding cats

Cats tested positive for GM1- or GM2-Gangliosidose, even they themselves are healthy and they are only carriers, shall not be permitted for breeding.
There are some organizations (like FIFe) which permit breeding GM-free x GM-carrier. To understand that breeding rule it needs a lot of imagination. The reason might be another rule, that only blue Korat are permitted to be registered as Korat in FIFe, all other colours are registered as not recognized Shorthair cats, thus restricting the gene-pool for a minority breed further more.

It would be interesting to get some statistical figures, how many Korat had been tested and how many carriers had been identified.