Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 8 Porphyrins and the Porphyrias
4 . Porphyria of Cats
Porphyria in cats was first reported in a male kitten
( Tobias, 1964 ). One of its three littermates and kittens
from a previous litter were also reported to have had the
same unusually discolored teeth. The kitten’s teeth were
brown and fluoresced red under ultraviolet light. Its urine
was amber colored and was qualitatively positive for uroporphyrin,
coproporphyrin, and porphobilinogen. There
was no evidence of anemia or photosensitization. These
cats had been kept indoors all their lives. One of these cats
was the propositus for a porphyric cat colony ( Glenn et al. ,
1968 ). The inheritance of the porphyria in these cats is a
simple autosomal dominant trait analogous to that seen in
swine.
Detailed studies of the porphyria in a family of Siamese
cats has been reported ( Giddens et al. , 1975 ) in which excessive
accumulation of URO I, COPRO I, and PROTO IX
were observed in erythrocytes, urine, feces, and tissues.
These cats had photosensitivity, severe anemia, and severe
renal disease. The researchers concluded that the principal
defect in these cats was a deficiency of UROgenIII-Cosyn
similar to CEP of humans and cows.
5 . Normal Porphyrias
All fox squirrels (Sciurus niger) have red bones caused
by the accumulation of URO I and COPRO I ( Flyger and
Levin, 1977 ). The fox squirrel porphyria resembles the
CEP of humans, cows, and cats by having a deficiency
of UROgenIII-Cosyn, type I porphyrins in their urine and
feces, and discolored bones, teeth, and tissues, which fluoresce
on exposure to ultraviolet light. There is increased
erythropoiesis but no apparent hemolytic anemia, no photosensitivity,
or any other clinically deleterious effects.
These relatively benign effects are most likely due to their
thick hair coats and nocturnal living habits. It is interesting
that an enzyme deficiency with serious health effects
in other animals should have evolved as a “ normal ” characteristic
in the fox squirrel. This is understandable when
one appreciates that CEP cattle always kept indoors and
protected from sunlight tend to thrive and reproduce
normally.
The UROgenIII-Cosyn deficiency is found only in
the fox squirrel and not in the closely related gray squirrel
( Sciurus carolinensis). Urine porphyrin excretion in the
fox squirrel is 10-fold greater than in the gray squirrel and
is markedly increased when erythropoiesis is stimulated by
bleeding. The UROgenIII-Cosyn of fox squirrel erythrocytes
is very heat sensitive, and this may indicate that its
CEP is due to an increased lability of the enzyme.
In the feathers of certain brightly colored birds (e.g.,
Touracos and in certain lower animals and microorganisms),
porphyrins accumulate but these appear to be normal
phenomena.
C . Hepatic Porphyrias
This group of diseases is seen only in humans as naturally
occurring diseases. They constitute the most common
group of porphyrias seen in humans. The salient features of
this group of porphyrias are also summarized in Table 8.2 .
As the name of this group implies, the predominant site of
the metabolic defect is localized in the liver, and the group
is further subdivided on the bases of their principal clinical
manifestations. Specific enzyme deficiencies have been
identified for all forms of hereditary porphyria ( Table 8.2 ).
As mentioned earlier, their genetic heterogeneity accounts
for the wide variety of symptoms.
1 . δ -Amino-Levulinic Acid Dehydratase
Porphyria
This rare hepatic form of porphyria has a marked deficiency
of the enzyme δ-amino-levulinic acid dehydratase
(ALA-D) in the homozygous state ( Brandt and Doss, 1981 ;
Doss et al. , 1979 ) and is referred to as ALA-D porphyria
(ADP). It is characterized by neurological symptoms without
skin photosensitivity. It is inherited as an autosomal
recessive trait. A similar though less marked ALA-D deficiency
that was without symptoms was reported ( Bird et al. ,
1979 ), and this is thought to be the heterozygous state of the
deficiency.
2 . Acute Intermittent Porphyria
Acute intermittent porphyria (AIP) is a common form in
humans characterized by acute abdominal pain and neurological
symptoms. Photosensitivity is not a feature of this
form. Most patients are not clinically affected unless some
form of aggravating factor is present. The attacks are precipitated
by a large number of causative factors, the principal
ones being barbiturates, sulfonamides, estrogens, and
alcohol. The disease occurs more commonly in the adult
female than in the male. The principal urinary finding is
the excretion of large amounts of ALA and PBG. This is
in keeping with the hereditary deficiency of UROgenI-Syn
(PBG-D) in this disease (Strand et al. , 1970). AIP is the
major autosomal dominant form of hepatic porphyria.
3 . Porphyria Cutanea Tarda
Porphyria cutanea tarda (PCT) is caused by a deficiency
of UROgen-D and presents as both a sporadic form and
a familial form. The sporadic form is the acquired form
of PCT and is the most common of all forms of human
porphyria. The familial form is inherited as an autosomal
dominant. As the name implies, the characteristic
clinical signs of PCT are the photosensitive lesions of the
skin. The disease occurs in mid to late adult life and common
precipitating causes of this disease are alcohol and