WHAT IS L2-HGA?


(L-2-hydroxyglutaric aciduria) in Staffordshire Bull Terriers is a
neurometabolic disorder characterised by elevated levels of
L-2-hydroxyglutaric acid in urine, plasma and cerebrospinal fluid. L-2-HGA
affects the central nervous system, with clinical signs usually apparent
between 6 months and one year (although they can appear later).
Symptoms include epileptic seizures, "wobbly" gait, tremors, muscle
stiffness as a result of exercise or excitement and altered behaviour. The
mutation, or change to the structure of the gene, probably occurred
spontaneously in a single dog but once in the population has been
inherited from generation to generation like any other gene. The disorder
shows an autosomal recessive mode of inheritance: two copies of the
defective gene (one inherited from each parent) have to be present for a
dog to be affected by the disease. Individuals with one copy of the
defective gene and one copy of the normal gene - called carriers - show
no symptoms but can pass the defective gene onto their offspring. When
two apparently healthy carriers are crossed, 25% (on average) of the
offspring will be affected by the disease, 25% will be clear and the
remaining 50% will themselves be carriers. The mutation responsible for
the disease has recently been identified at the Animal Health Trust. Using
the information from this research, we have developed a DNA test for the
disease. This test not only diagnoses dogs affected with this disease but
can also detect those dogs which are carriers, displaying no symptoms of
the disease but able to produce affected pups. Carriers could not be
detected by the tests previously available which involved either a blood or
urine test detecting elevated levels of L-2-hydroxyglutarate or magnetic
resonance imaging. Under most circumstances, there will be a much
greater number of carriers than affected animals in a population. It is
important to eliminate such carriers from a breeding population since they
represent a hidden reservoir of the disease that can produce affected
dogs at any time. The test is available now and information on submitting
samples is given below. Breeders will be sent results identifying their dog
as belonging to one of three categories:


CLEAR: the dog has 2 copies of the normal gene and will neither develop
L-2-HGA, nor pass a copy of the L-2-HGA gene to any of its offspring.


CARRIER: the dog has one copy of the normal gene and one copy of the
mutant gene that causes L-2-HGA.  It will not develop L-2-HGA but will
pass on the L-2-HGA gene to 50% (on average) of its offspring.


AFFECTED: the dog has two copies of the L-2-HGA mutation and is
affected with L-2-HGA.  It will develop L-2-HGA at some stage during its
lifetime, assuming it lives to an appropriate age.


Carriers can still be bred to clear dogs. On average, 50% of such a litter
will be clear and 50% carriers; there can be no affecteds produced from
such a mating. Pups which will be used for breeding can themselves be
DNA tested to determine whether they are clear or carrier.


What will be produced with the different
combinations if clear, carrier and affected dogs:

clear x clear all puppies will be clear, no need to test puppies!

clear x carrier 50% puppies will be clear,50% puppies will be carrier, test all
puppies to be using for breeding

clear x affected all puppies will be carriers, no need to test puppies

carrier x carrier 25% puppies will be clear, 25% puppies will be affected,
50% puppies will be carrier

carrier x affected 50% puppies will be affected, 50% puppies will be carriers

affected x affected all puppies will be affected


Colonial Staffy's will only breed Clear to Clear dogs.
No carriers or affected dogs will ever be used in our
program.  All of our breeding stock has either been
tested clear or is clear by parentage.