Q: "Wow!  I read and reread your little genetic thesis last night, but I
don't understand why you don't think protine stones are a problem.  If
ferrets were eating low protein food, wouldn't you expect it to show up
when they started eating high protein foods?  How do you know it is not
a problem with most ferrets?  Are you God?"
 
A: No, just Bob.  I hit my hand with hammers, drop tree branches on my
head, slide off roads on my bicycle, jump to boulders in a creek not
realizing they are covered with ice, jerk my head into nails, and even,
to my great embarrassment, run over my own foot while helping a lady
push her car off the road.  I'm not kidding; a week ago I was carrying a
stack of books about as high as my nose, thought I had about a foot to go
before I reached the stairs, and discovered you can spastically hop down
stairs carrying books, but you can't avoid the floor at the bottom.  One
of the books was Asdell's Patterns of Mammallian Reproduction, and it
made quite the impression on me.  God may be clumsy, creating Scientific
Creationists, okra, mushrooms, and eggplants, but he is nowhere as clumsy
as I am.  Of course, if God were that clumsy, it would explain the Big
Bang, Paris Hilton, AND George Bush.  However, as much as I appreciate
your nomination to the position, there is already a demigod on this list,
and that's the BIG guy.  Be careful and dont incur his ire, or you might
burn in FMHell.  (Boy, that was a long build-up to a bad pun.)
 
Cystine stones have been found in numerous species, including humans,
more than 60 breeds of dogs, cats, maned wolves, captive lions, and
arctic fox.  There is some evidence they have occurred in some animals
raised for the fur industry, specifically arctic fox and raccoon dogs.
Cystine stones tend to occur in carnivores because they generally have
acidic urine from consuming meat protein; it is possible herbivores could
have them, but since high plant consumption generally results in alkaline
urine, they probably occasionally have the problem but it just doesnt
form the stones you see in carnivores.
 
The problem is caused by cystinuria, which is a disease caused by a
metabolic defect that inhibits or makes difficult the movement of certain
amino acids into or out of cells, particularly those of the kidney.
Normally, amino acids and some other substances are filtered out of the
blood and reclaimed from the urine in the kidneys.  When you have
cystinuria, the amino acids cystine, ornithine, lysine, and arginine
(collectively called COLA), are not reabsorbed and urine concentrations
can become very high.  Cystine is not as soluble when the urine is acidic
and it can precipitate out, creating everything from microscopic
crystals, to large stones (calculi); the stones can form in the kidney
or the bladder.
 
You cannot catch cystinuria; you might get it by having a gene mutation,
but probably you inherit it from your parents.  There are at least two,
maybe three different genetic defects that can result in the disease; one
researcher suggesting perhaps four could be responsible.  Most forms of
the disease are autosomal recessive, which means you need two copies of
the gene to have the disease.  Another form of the disease is probably
linked to the X-chromosome and recessive, but that hasn't been
conclusively proven.
 
Forget for a moment that we are talking about cystinuria--suppose we
are talking about sables and albinos.  While albinism can be caused by
several genetic problems, the most common form is autosomal recessive,
just like cystinuria, so it is a good example.  The genes for color in
ferrets are different than those that code for albinism, so forget color
and just consider being able to make pigment (A) compared to not being
able to make pigment (a).  Every animal has two copies of each gene, one
from each parent.  So, in terms of pigmentation, a ferret could be AA,
it could be Aa, it could be aA, or it could be aa; those are the only
possibilities.  Because albinism is autosomal recessive, the only way
you can have it is by having the aa genes; AA, Aa, and aA genes result
in pigmented animals.  In a large population, this means the ratio of
pigmented to albino animals is 3:1.  Put another way, if albinism was
widespread in the population, you would expect about 1/4th of all ferrets
to be albinistic.
 
See how it works?  X-linked recessive traits are similar, except because
females have two X-chromosomes, they need two genes to have the disease.
Males, on the other hand, only have one X-chromosome, which means all
they need is a single bad gene and they will get the disease.  In this
case, because males only pass X-chromosomes to their daughters, any male
with the disease inherited it from their mother, and any female from both
mother and father.  Males therefore contract the disease at a far higher
rate than females.
 
Now, to muddy the waters and make the disease all the more interesting;
in the autosomal recessive form of the disease, both males and females
have the disease in approximately equal numbers.  However, the disease is
diagnosed in males in disproportionate amounts; about 90% of the stones
are collected from males.  The reason for this is thought to be due to
the mechanics of the male urinary tract; some combination of prostate,
bacula, length of urethra, hormones--they are not exactly sure why, but
males either form more stones than females, or the stones pass easier in
females and are never collected.  This doesn't mean females dont have
the disease; it just means they are not diagnosed.  They could be
spilling COLA proteins all their life, but unless a stone blocks
something, no one may be the wiser.
 
Before I explain why these few facts tells us that cystinuria is not
in the general population gene pool, let me talk about the disease a
little.  Cystinuria is a metabolic problem that makes it hard for the
COLA proteins (C = cystine, remember) to be reabsorbed from the kidney.
If you have cystinuria, then you have cystinuria, regardless if you are
throwing stones or remain undiagnosed.  While there may be some obscure
forms that might, possibly, perhaps become exhibited in later life
stages, if you have the two common forms, either autosomal recessive, or
X-linked recessive, you have it at the beginning of your life as well as
the end.  There are tests to screen for this, while they may not have
been adapted to ferrets, they can be developed there as well with little
difficulty.  More important, the morbidity and possible mortality of the
disease is associated with the formation of stones and subsequent
blockage of portions of the urinary tract.  All treatments center around
the prevention of stones and blocked urinary tracts.
 
This is the extremely important part.  There is NO evidence that kibble
is a safer food to feed compared to a high protein meat product.  In
fact, it is likely kibble may cause as many or more problems than any
other food.  Why?  The reason the stones form is because they have
relatively low solubility in acidic urine, so when animals or people
become dehydrated, cystine levels can reach the critical point where they
start precipitating out of solution, making the stones that cause so much
trouble.  In cystinuria, WATER is a drug!  You recognize the implication
of this, don't you?
[Posted in FML issue 4787]