PK -anemia on vapaaehtoisella testauksella saatu kuriin ja kissojen taustat tunnetaan. Yleisesti ottaen suomalaiset kasvattajat DNA -testauttavat kissansa PK- anemian varalta eivätkä tuota sairaita pentuja. Paljon on jo linjoja joissa vanhempia ei enää edes tarvitse testata, koska PK- anemia testaukset ovat tehty esivanhemmille ja ne ovat terveitä. PK -anemia on siis resessiivisesti periytyvä mutaatio, joka on suhteellisen helppo nykyisen DNA testauksen tultua pyyhkäistä menneisyyteen.
Joissakin vähenevässä määrin eteen tulevissa tilanteissa kasvattaja päätyy käyttämään PK- anemian kantajaa. Tällöin toinen vanhemmista on aina terve, jolloin ei sairaita jälkeläisiä pääse syntymään. Näiden nykyään harvinaistuneiden tapausten tausta on se, että vaikka toinen kissoista on kantaja, sen geneettinen monimuotoisuus voi tuoda jotain rodulle joka on suhteellisen pieni. Ja se on ollut hyväksyttävää, kunhan tulevat sukupolvet eivät kärsi eli jatkoon valitaan terve yksilö ja kaikki pennut testataan.
Mutta onneksi tosiaan olemme jo niin pitkällä tässä tilanteessa, että näitä "kantaja x terve" -astutuksiakaan tehdään enää todella harvoin.
Kaikki Bastian's kasvatukseen käytettävät naaraat tai niiden vanhemmat ovat testattu DNA -testuksella terveiksi PK -anemian osalta..
Kuu-Katjaana
Following international collaboration, a set of questions on
pyruvate kinase (PK) deficiency were compiled and co-ordinated by me,
then put to Dr Urs Giger, who had earlier kindly agreed to answer them,
for publication in the August 2004 issue of The Abyssinian Breeder
magazine. Dr Giger is a world-leading scientist in this field, who
researched the means of inheritance and established the DNA test that
can be used to determine whether a cat is normal, a carrier or affected
by PK deficiency. Affected cats may suffer from cyclical anaemia (see
below) Dr Giger’s CV is given at the end of this Q
&A, just after a note on the method of inheritance and its
consequences.
The questions are grouped and sequenced; Dr Giger’s answers
were provided in mid June 2004, and appear below each question, with
borders around them for differentiation. The questions arise because PK
deficiency carriers – and even some affected cats –
have appeared among Abyssinians and Somalis in the United States,
Australia, New Zealand, Denmark, Germany and elsewhere in Europe. Some
of us have had all our cats tested. Once carriers (if any) have been
identified, steps can be taken to eliminate PK deficiency by keeping
normal offspring from carrier-to-normal or (generally inadvertent)
carrier-to-carrier matings. In this fashion, all lines and genetic
diversity can be preserved. For more information on the implications of
PK deficiency and how to test for it, go to
http://www.vet.upenn.edu/research/centers/penngen/services/deublerlab/pk.html
and follow the links given on that page. Additional, though slightly
out of date information is available at
http://www.abyssinianbc.org/PKDef_ursgeiger.htm (sorry about
the mis-spelling of Dr Giger’s name but that’s the
address).
Finally, those of us who have been through the hoops know to spell out
“deficiency” in full, otherwise confusion can arise
because the abbreviation “PKD” is customarily used
to denote “Polycystic Kidney Disease”, totally
different from PK deficiency and not known to occur among Abyssinians
or Somalis.
George
Kennedy
a. How exactly
are results measured? (Is it a simple presence
or absence of ’something’, a particular
’something’ falling within certain percentages of
in a scale, a particular spectrograph pattern?)
This is a DNA test that
specifically detects the presence or absence of the mutant and normal
allele (gene) for PK deficiency. After amplifying the DNA around the
known PK mutation we are using a specific digestion procedure to
differentiate the mutant and normal allele by size on a gel. A cat can
either show only the normal allele (2 copies), or only the mutant
allele (2 copies of the mutant, homozygous affected, or can have one
normal and one mutant allele. Thus this is a definitive test. One note
when submitting cheek swabs: we do need cheek cells rather than saliva,
thus you must rub the brush on the inside cheek and follow the
instructions carefully.
b. What
proportion of
test samples comes from outside the United
States?
Currently
we are the only lab testing for this PK mutation and after initially
receiving exclusively samples from within the US, about 30% come from
Europe and Australiac.
c. Do you envisage the
tests becoming available at
other laboratories, perhaps even outside USA?
Yes; however, shipping
cheek swabs is easy, testing is not done frequently, and as long as we
are getting the test results we can follow the frequency of the mutant
allele
a. Roughly how
many Abys and Somalis have been tested, and what proportion of these
were found normal, carriers and affected?
About 1000
Abyssinians and Somalis have been tested since 1998, and the mutant
allele frequency is very high at about 10 to 20% due to inbreeding
practices. In humans diseases with a frequency of 1% are considered
common.
b. Any thoughts on why PK
deficiency in cats is encountered
almost exclusively among Abyssinians and Somalis?
It appears likely that
the mutation has a arisen in one of these breeds; they have the same
mutation and thus all of these cats are related. High mutation
frequencies are recognized in various breeds in cats and dogs as well
as ethnic and geographical areas in people. For instance a high
frequency for PK has been seen in the Amish populationc.
c. Why have so few cats
(zero in Denmark, apparently) been diagnosed with PK
deficiency; there must be affected cats in different lines, so why
haven’t we met them as ill cats?
The number of
cats tested in
Denmark is small; it is well possible that these cats in Denmark are
from a line free of the mutation. If there are carriers, matings
between carriers may not have been done. Furthermore, only one quarter
of a carrier-to-carrier mating will be affected and indeed not every
PK-deficient cat will develop clinical signs or may only show
intermittent mild signs or the signs are thought to be caused by
something else, like haemobartonellosis or immune-mediated haemolytic
anaemia.
a. How likely is
it that an affected cat will suffer from anaemia during its life?
This is not known, because many cats have been treated for anaemia
before a diagnosis is made and others are screened for because of
related cats are anaemic. Thus our sample pool is biased. Following PK
deficient cats however indicates that they remain most of the time
slightly anaemic. Cats can readily compensate for the anaemia
presumably due to their life style.
b. What are the first
clinical signs that an affected cat usually shows other than anaemia;
are there other signs as well?
The clinical signs vary and are unspecific, but lethargy, depression
and lack of appetite may be observed. The gums may be pale and rarely
icteric and the abdomen may be enlarged. Indeed, some PK-deficient cats
are incidentally found to have been treated for other potential
diseases including haemobartonellosis and immune-mediated haemolytic
anaemia. In particular, some of the potent immunosuppressive agents are
not helpful and can be harmful.
c. Is it beneficial to
give affected cats special diets right from the start, e.g., high doses
of iron?
There seems to be no problem with iron absorption and storage or
utilization. In fact the body iron stores are adequate (normal) to
increased, and further supplementation may cause hepatic and splenic
organ failure and thus is not advisable. However, it is advisable to
keep the PK-deficient cat on a well balanced diet to avoid any untoward
stress and gastrointestinal upset. It is imperative to provide good
care, a stress free environment, and routine health check ups.
d. What is the best
treatment once the first symptoms start, or the best course of action
for my vet to take?
The best treatment has not been scientifically determined. However, the
diagnosis of PK deficiency will help the vet to avoid certain
unnecessary or even harmful medications. Some cats may require some
prednisone or even a splenectomy if the crises become more frequent. In
a crisis they may also need a blood type compatible transfusion.
e. What are the prospects
of a cat diagnosed as affected, for length and quality of life?
Many cats can live good lives for many years, with the oldest reaching
thus far 12 years.
f. If you have bred from
an affected cat to say a carrier, or carrier to carrier, and you know
you have affected kittens, is it best just to pet these kittens out
free, and tell the new owners, or keep them for observation, rather
than euthanasing the kittens?
Affected cats should best be not bred. In case this has happened they
should be sold and placement should be carefully considered as it can
be a hardship for an owner to see the cat suffer and to pay for the
medical care of the cat. I have adopted one of the affected cats and
have enjoyed her tremendously over the past several years, with TLC as
the only treatment albeit she is always anaemic.
g. Just how important is
PK deficiency within the two breeds? This question is being asked
because there are sceptics out there who don’t think it is
important??
Just like I discovered the blood type issue in the neonatal Abyssinians
and Somalis hopefully have help many breeders to prevent neonatal
isoerythrolysis (NI, hemolysis of the newborn), I am convinced that
testing for PK and informed breeding away from
PK will improve the health of the breeds affected and prevent further
suffering. Based upon our - albeit biased -frequency within the two
breed this is an important health issue.
NOTE No questions were asked on
inheritance, since it was established by Dr Giger that pyruvate kinase
(PK) deficiency is carried by a recessive gene and hence the usual laws
of heredity apply, viz.:
::normal X
normal matings--> always produce normal offspring
::normal X
carrier matings--> will on average produce 50%
normal and 50%
carrier offspring
::carrier X
carrier matings-- will on average produce
25% normal, 50% carrier and 25% affected offspring
::affected X
normal matings-- will produce offspring that are
all carriers
::affected X
carrier matings-- will on average produce 50%
carrier and 50% affected
offspring
::affected X
affected matings-- will always produce affected
offspring
only affected cats may
get anaemia not carriers
Urs Giger
received his veterinary degree from the University of Zürich,
Switzerland, where he also pursued his initial clinical training in
small animal medicine and surgery and a doctoral thesis on the
orthopaedic correction of canine hip dysplasia. In 1981, he moved as a
postdoctoral fellow to the United States where he subsequently
completed a postdoctoral fellowship and residency in small animal
medicine at the University of Florida.
He then joined the faculty of the School of Veterinary Medicine at the
University of Pennsylvania in Philadelphia and has been over the years
a clinician in the Medicine, Oncology, and Pediatrics/Genetics Service.
He is currently the Charlotte Newton Sheppard Professor of Medicine and
Chief of Medical Genetics and has a secondary professorship at the
University of Zürich. He is a diplomate of the American and
European College of the Veterinary Internal Medicine and is heading the
Pediatrics and Genetics Clinic, the Metabolic Genetics Laboratory, the
Josephine Deubler Genetic Disease Testing Laboratory, and the
Transfusion Medicine Center at the University of Pennsylvania. His
clinical and research expertise and interests are in hereditary and
hematologic disorders of small animals and are reflected in over 150
original publications as well as many more reviews, chapters, and
scientific abstracts.
He was the recipient of the International Scientific Lifetime
Achievement Award in 2002 from the World Small Animal Veterinary
Association and the John McCoy award in 2004.
This page was last updated on 22-Jun-04
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