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

IV. Porphyrias
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estrogens. The disease can be successfully treated by the
avoidance of alcohol and estrogens. There is a decrease
in hepatic UROgen-D in both forms, but the enzyme deficiency
is found in extrahepatic tissues only in the familial
form ( Pimstone, 1982 ). In the sporadic form, erythrocyte
UROgen-D activity is normal, whereas in the familial
form, erythrocyte UROgen-D is less than 50% of normal
( McManus et al. , 1988 ). The erythrocyte UROgen-D assay
is difficult and not readily available, therefore indirect
means of distinguishing the sporadic form from the familial
are used. One of the most simple, indirect methods
has been to assay the plasma γ -glutamyltransferase activity
(GGT). Sporadic PCT has a significant increase in
GGT, whereas the familial form has normal GGT activity
( Badcock et al. , 1993 ). Furthermore, the ratio of fecal
COPRO III:COPRO I when combined with the plasma
GGT was found to give an even more accurate differentiation
of the sporadic form from the familial form ( Badcock
et al. , 1995 ).
4 . Hepatoerythropoietic Porphyria
Hepatoerythropoietic porphyria (HEP) is a form that clinically
resembles congenital erythropoietic porphyria (CEP),
but there is a severe deficiency of UROgen-D as in PCT.
It is thought to be the homozygous form of familial PCT.
HEP is characterized by a severe photosensitivity, but there
is no liver involvement.
5 . Harderoporphyria
This is a rare form of porphyria in which the propionate
group on the A ring only is converted to a vinyl group. The
normal next step of B ring conversion is somehow disrupted.
There is a deficiency of COPROgenIII-Ox, but the
mechanism explaining why the groups on both rings are
not oxidized is unknown.
6 . Hereditary Coproporphyria
Hereditary coproporphyria (HCP) is clinically similar to
PCT with a mild cutaneous photosensitivity, and it may
also have neurological symptoms as in AIP. Like AIP, HCP
is commonly precipitated by drugs and alcohol. As in harderoporphyria,
COPROgenIII-Ox is the deficient enzyme.
7 . Variegate Porphyria
The symptoms of variegate porphyria (VP) are generally
more variable than the other forms but in most cases,
acute abdominal pain and photosensitivity are seen. VP
is most common among the South African white population.
VP is inherited as an autosomal dominant. There is a
deficiency of PROTOgenIII-Ox, which can be observed in
cultured fibroblasts and in leukocytes of VP patients. Hift
et al. (2004) found plasma fluorescence scanning to be a
more sensitive and specific test for VP than fecal porphyrin
analysis.
D . Porphyrinurias (Acquired Toxic
Porphyrias)
1 . Chemical Porphyrinurias
The two major forms of the porphyrinurias are those due
to organic chemical intoxication and to heavy metal poisonings,
mainly lead. Experimentally, hexachlorobenzene
(HCB) ( Elder et al. , 1976 ), 2,3,7,8-tetrachlorodibenzop-dioxin
(TCDD) ( Elder and Sheppard, 1982 ), allylisopropylacetylcarbamide
(Sedormid) ( Schmid and Schwartz,
1952 ), or dihydrocollidine (DHC) ( Granick and Urata, 1963 )
has been used to produce the hepatic forms of porphyria.
2 . Lead Poisoning
Lead poisoning occurs in all domestic animals and is a significant
clinical problem, particularly in the dog. In the dog
as in other animals, the principal clinical features are related
to the gastrointestinal and the nervous systems. Anemia is
usually seen only in the long-standing chronic lead toxicities.
The anemia has certain features that suggest lead
poisoning but are not diagnostic. The anemia is a mild to
moderate normocytic normochromic anemia with basophilic
stippling and nucleated erythrocytes (NRBC) out of proportion
to the degree of anemia. Zook et al . (1970) considered
that 15 stippled cells per 10,000 erythrocytes is suggestive
of and that 40 stippled cells per 10,000 erythrocytes
is diagnostic of lead poisoning in the dog. Stippling is
thought to be accumulated ribosomal RNA aggregates that
have not been normally degraded to their nucleotides and
subsequently dephosphorylated by pyrimidine-5 nucleotidase
(P5NT). Lead has been shown to decrease the activity of
the dephosphorylating enzyme, P5NT in humans ( Valentine
et al. , 1976 ) and in calves ( George and Duncan, 1982 ).
Lead is known to have widespread toxic effects on
sulfhydryl-, carboxyl-, and imidazole-containing proteins
that would include enzymes, cell proteins, globins, and
membrane proteins ( Fell, 1984 ). However, only a few are
altered specifically and significantly to be of diagnostic
value. Globin synthesis and therefore hemoglobin synthesis
is disrupted, and this is the major mechanism of the anemia
of lead poisoning. The anemia, however, occurs late in
chronic lead poisoning, and its nonspecific nature makes it
of less diagnostic importance than is usually attributed to it.
A major focus is on the enzyme systems of heme synthesis
because several of the enzymes are very sensitive in
early exposure to small quantities of lead. The most sensitive
are ALA-D and FER-Ch, and these enzymes and their
accumulated substrates are widely used as screening tests