Chemical Pathology 7 - Porphyrias

Question 1

What is haem?

Answer 1

Tetrapyrole rings surrounding a central iron

Question 2

Roughly summarise the pathway of haem production

Answer 2

ALA + ALA –> PBG
PBG –> HMB
HMB –> EITHER uroporphyriogen 1 or 3
Uroporphyrinogen 3 –> haem

Question 3

By what 2 factors are porphyrias classified?

Answer 3

Acute/ non-acute

Neurovisceral or cutaneous

Question 4

What is the cause of cutaneous symptoms in some porphyrias?

Answer 4

Porphyrin precursors build up under the skin and react with UV

Question 5

Which toxic product leads to neurovisceral symptoms in porphyria?

Answer 5

5-ALA

5-Aminolevulinate

Question 6

What is the most common porphyria?

Answer 6

Porphyria cutanea tarda

Question 7

What is the most common porphyria in children?

Answer 7

Erythropoietic protoporphyria

Question 8

What are the symptoms of ALA synthase deficiency?

Answer 8

Weirdly, doesn’t cause porphyria!

Instead, causes an X-linked sideroblastic anaemia

Question 9

What are the 2 types of acute neurovisceral porphyria, which enzyme deficiency causes each, and how can they be clinically differentiated?

Answer 9

Acute intermittent porphyria (most common) = HMB (Hydroxymethylbilane) synthase deficiency - causes ATTACKS
ALA dehydratase porphyria = PBG (Porphobilinogen) synthase deficiency - more one acute episode than numerous attacks

Question 10

What are the symptoms of the acute neurovisceral porphyrias?

Answer 10

Motor neuropathy
Psychiatric symptoms
Severe abdominal pain

Question 11

What is the most likely cause of an acute intermittent porphyria ‘attack’?

Answer 11

Drug that is CYP450 inducer

Question 12

How can acute porphyria be diagnosed?

Answer 12

Urine left in light changes colour

Question 13

How should acute intermittent porphyria be managed?

Answer 13

Avoid attacks (adequate nutrition, precipitant drugs, prompt treatment)
IV carbs OR
IV haem arginate

Question 14

Recall 2 forms of porphyria that have acute neurovisceral AND cutaneous symptoms

Answer 14

Hereditary coproporphyria

Variegate porphyria

Question 15

How do the cutaneous effects of porphyrias usually present and why?

Answer 15

Blistering on back of hands (most exposed to UV)

Question 16

Recall the 3 forms of non-acute porphyria, and which of these conditions causes blistering

Answer 16

Congenital eryhtropoietic porphyria (blistering)
Porphyria cutanea tarda (blistering)- most common
Erythropoietic protoporphyria (non blistering)- most common in kids

Question 17

How can erythropoietic protoporphyria be diagnosed?

Answer 17

Undetectable in urine so will need to send blood

Question 18

What is the most common cause of porphyria cutanea tarda?

Answer 18

Liver disease