Porphyrias (Schalm 28)

Question 1

What group name do we give to diseases arising from defective heme production?

Answer 1

Porphyria’s

Question 2

What is the rate-limiting enzymatic step in heme synthesis?

Answer 2

ALA synthase (the first step in the mitochondria), which converts succinyl CoA and glycine to delta-aminolevulinic acid

Question 3

Which two enzymes in heme synthesis are inhibited by lead toxicity?

Answer 3

ALA dehydratase
Ferrochelatase

Question 4

What two tissues produce the most heme?

Answer 4

Bone Marrow (approximately 80%)
Liver

Question 5

Name 6 hemoproteins that incorporate heme

Answer 5

Hemoglobin
Myoglobin
Cytochrome
Catalases
Peroxidases
Endothelial nitric oxide synthase

Question 6

Which of the heme precursors are porphyrins?

Answer 6

Only protoporphyrin IX is a true porphyrin

Question 7

What are two characteristics of porphyrins?

Answer 7

Absorb light at 400-410nm
Cause cell damage and discoloration of tissues

Question 8

What are four possible clinical signs of porphyrias?

Answer 8

Discoloration of tissues
Cutaneous photosensitivity lesions
Red-orange staining of dentine in the young
Urine discoloration

Question 9

How do porphyrins cause cutaneous lesions?

Answer 9

Absorb UV light
Transition to excited state
Transfers energy to cell structures or oxygen, forming ROS and oxidation

Question 10

How do porphyrias cause hemolytic anemia?

Answer 10

High concentrations of porphyrins are thought to alter erythrocytes resulting in early removal from circulation
(As supported by decreased RBC survival time in porphyria cows without exposure to sunlight)

Question 11

While neurovisceral signs are only reported in humans, which heme precursors are thought to be neurotoxic?

Answer 11

Delta-ALA
Porphobilinogen (PBG)

Question 12

What test may confirm the presence of porphyrins?

Answer 12

Exposure to UV light
(Wood’s lamp or other UV source with Soret band (400-410nm) creates intense pink or red fluorescence on teeth or urine

Question 13

If a lab is found to test for porphyria, what must be done to protect the sample?

Answer 13

Protect the sample from light exposure

Question 14

Briefly describe the ALA dehydratase reactants and products. What are two causes and manifestations of decreased ALAD activity?

Answer 14

Two molecules of ALA are used to form PBG (porphobilinogen)
ALAD deficient porphyria (rarely reported in animals)
Lead toxicity (inhibits ALAD)
High ALA -> coproporphyrin and increased erythrocyte protoporphyrin lead to acute neurological symptoms

Question 15

Acute intermittent porphyria is associated with decreased activity of what enzyme? In which species has it been reported?

Answer 15

Decreased hydroxymethylbilane synthase activity (converts porphobilinogen, PBG, to hydroxymethylbilane)
Reported in cats (4 genetic lines) and humans
Urine may become dark red during an attack - elevated PBG in urine is the most significant finding for tentative diagnosis. Cats were identified by erythrodontia and red urine.

Question 16

Congenital erythropoietic porphyria (CEP) causes markedly decreased activity of what enzyme?

Answer 16

Decreased uroporphyrinogen synthase activity (which transforms hydroxymethylbilane to uroporphyrinogen III)

Question 17

Name the reactant and product of the uroporphyrinogen decarboxylase enzymatic reaction

Answer 17

Decarboxylation of uroporphyrinogen to coproporhyrinogen

Question 18

Name the reactants and products of the coproporphyrinogen oxidase enzymatic reaction

Answer 18

Conversion of coproporphyrinogen III to protoporphyrinogen IX

Question 19

Name the reactants and products of the protoporphyrinogen oxidase enzymatic reaction

Answer 19

Oxidation of protoporphyrinogen IX to protoporphyrin IX

Question 20

What enzyme activity is decreased in erythropoietic protoporphyria?

Answer 20

Ferrochelatase

Question 21

Congenital erythropoietic porphyria has been shown in what species?

Answer 21

Cats
Cattle
Poss pigs, white rabbit, hedgehog

Question 22

What decreased enzyme activity is characteristic of congenital erythropoietic porphyria?

Answer 22

Uroporphyrinogen synthase

Question 23

What prophryins are increased in congenital erythropoietic porphyria, and where are they found?

Answer 23

Uroporphyrin I and coproporphyrin I in the urine, plasma, and erythrocytes

Question 24

Low UROS activity is ubiquitous in what species, and how is it manifested clinically?

Answer 24

Fox squirrels. Fox squirrels have browner bones and teeth which fluoresce pink, but the squirrels are not otherwise clinically affected and are not anemic.

Question 25

Porphyria Cutanea Tarda is the result of a mutation in which enzyme? What species are affected?

Answer 25

Uroporphyrinogen decarboxylase
A flock of German blackface sheep
Possible Belgian Landrace pig at slaughter

Question 26

Erythropoietic protoporphyria is most common in what cattle breed? What are the symptoms?

Answer 26

Limousine cattle
Cutaneous lesions (crusting, exudation, ulceration, alopecia)
Not anemic, no discoloration of teeth and urine

Question 27

Markedly high concentrations of protoporphyrin in erythrocytes and feces is characteristic of which porphyria?

Answer 27

Erythropoietic protoporphyria (EPP); caused by aberrant ferrochelatase activity

Question 28

What is the inheritance pattern of EPP? Where is genetic testing available?

Answer 28

Autosomal recessive
North American Limousine Foundation (also Canadian and Australian)