Porphyrias

Question 1

What is a porphyria?

Answer 1

Disorder caused by deficiency in an enzyme of haem synthesis

Question 2

What does this lead to and how can it manifest itself?

Answer 2

Build up of toxic haem precursors

Manifest as:

• Acute neuro-visceral attacks
• Acute or chronic cutaneous symptoms

Question 3

What is the structure of haem?

Answer 3

Organic heterocyclic compound
Fe2+ in the centre
4 pyrrolic rings around the iron
Carries oxygen

Question 4

Where does haem synthesis begin?

Answer 4

In the mitochondrion

Question 5

Where is ALA generated?

Answer 5

In the mitochondrion

Question 6

What converts ALA to PBG?

Answer 6

PBG synthase

Question 7

What converts PBG to HMB?

Answer 7

HMB synthase

Question 8

What is required for HMB to be converted to uroporphyrinogen 2?

Answer 8

Uroporphyrinogen 3 synthase

Question 9

If uroporphyrinogen 3 is not present, what is HMB converted to?

Answer 9

Uroporphyrinogen 1

Question 10

What enzyme converts Uroporphyrinogen 3 to coproporphyrinogen 3?

Answer 10

Uroporphyrinogen decarboxylase

Question 11

Where does coproporphyrinogen 3 go after it has been produced?

Answer 11

Back into the mitochondrion

Question 12

What converts coproporphyrinogen 3 to protoporphyrinogen 9?

Answer 12

Coproporphyrinogen oxidase

Question 13

What converts protoporphyrinogen 9 to protoporphyrin 9?

Answer 13

Protoporphyrinogen oxidase

Question 14

What is protoporphyrin 9?

Answer 14

Haem without the iron

Question 15

Which enzyme converts protoporphyrin 9 to haem?

Answer 15

Ferrochetalase

Question 16

Where can the enzyme deficiencies be (in the body)?

Answer 16

Erythroid

Hepatic

Question 17

What is the most common type of porphyria?

Answer 17

Porphyria cutanea tarda

Question 18

What is the most common type of porphyria in children?

Answer 18

Erythropoietic protoporphyria

Question 19

What does ALA synthase deficiency show on a blood film?

Answer 19

Sideroblasts

X-linked sideroblastic anaemia

Question 20

Which enzyme is deficient in acute porphyria?

Answer 20

PGB synthase

Leads to accumulation of ALA
Very rare
Neurological symptoms + abdominal pain

Question 21

Which enzyme is deficient in acute intermittent porphyria?

Answer 21

HMB synthase

Autosomal dominant

Neurovisceral attacks
No skin symptoms

Question 22

What can precipitae acute intermittent porphyria?

Answer 22

ALA synthase inducers (barbiturates, steroids, ethanol, anticonvulsants)
Stress
Reduced caloric intake
Endocrine factors

Question 23

How are attacks of acute intermittent porphyria treated?

Answer 23

IV carbohydrate (inhibits ALA synthase)
IV haem arginate (turns off haem synthesis through negative feedback)

Question 24

Which two acute porphyrias also have skin manifestations?

Answer 24

Hereditary coproporphyria

Variegate porphyria

Question 25

Where does blistering typically occur in hereditary coproporphyria?

Answer 25

Backs of hands

Appear hours/days after sun exposure

Question 26

What happens to the urine PBG in all types of acute porphyria?

Answer 26

Raised

Question 27

What do the urine and faeces porphyrin levels look like in the 3 types of acute porphyrias?

Answer 27

HCP + VP = high

AIP = not high

Question 28

What do non-acute porphyrias present with?

Answer 28

Skin lesions

No neurovisceral manifestations

Question 29

What tends to bring on the skin lesions in non-acute porphyrias?

Answer 29

Sun exposure

Question 30

Which non-acute porphyria is NON-BLISTERING?

Answer 30

Erythropoietic protoporphyria

Tends to present with photosensitivity, burning, itching and oedema after sun exposure

Question 31

What is the triad of symptoms of acute porphyrias?

Answer 31

Abdominal pain
Neurological symptoms
Psychiatric symptoms

Question 32

During acute porphyria, what is the most useful sample to send?

Answer 32

Urine (PBG)