Porphyria

Question 1

Haem structure + function

Answer 1

Tetrapyloric (4x pyloric rings)

Made in all cells - most important RBCs (Hb) + liver (CYP450) + other cells e transport chain for respiration

Question 2

Problem in porphyria

Answer 2

Deficiency in haem synthesis enzyme = build up of toxic pre-cursors in brain / skin + increased excretion in urine / faeces

Question 3

Rate-limiting step of haem synthesis

Answer 3

ALA synthase (catalyses Succinyl-coA + Glycine > ALA)

Question 4

Haem breakdown pathway

Answer 4

1. Succinyl-coA + Glycine > ALA (ALA synthase). ALA is then transported out of the mitochondria
2. PBG synthesis by PBG synthase
3. HMB synthesis by HMB synthase
4. U-III synthesis by U-III synthase
5. C-III synthesis by U-III decarboxylase
6. Protoporphyrinogen IX synthesis by C-oxidase
7. Protoporphyrin-IX synthesis by proto-oxidase
8. Haem synthesis by ferrochetelase

Question 5

Negative feedback in haem synthesis

Answer 5

Protoporphyrinogen + C-III upon HMB synthase

Question 6

3 manifestations of porphyria symptom

Answer 6

1. Acute neurovisceral attack
2. Non-acute cutaneous
3. Increased pre-cursor excretion in urine / faeces

Question 7

Acute neurovisceral attack symptoms

Answer 7

Neurotoxicity - N+V, severe pain, hypotension, tachycardia
ALA +/- PBG build-up
Triggered by alcohol, stress, NSAIDs, co-trimoxazole, steroids, barbiturates, COCP

Question 8

Cutaneous symptoms

Answer 8

Skin lesions - blistering or non-blistering in areas exposed to sunlight
Not ALA + PBG

Question 9

What happens to haem pre cursors down the pathway?

Answer 9

Increased double bonds -> increased stability -> reduced solubility (faecal > urine excretion)

Question 10

Acute symptoms only

Answer 10

AIP, ADA

Question 11

Acute + cutaneous symptoms

Answer 11

HCP, VP (Blistering)

Question 12

Cutaneous symptoms only

Answer 12

CEP, PCT (Blistering)

EPP (Non-blistering)

Question 13

Acute symptoms only
Most common porphyria
Raised ALA + PBG in urine 
HMB synthase deficiency
Port wine urine
AD inheritance

Answer 13

Acute Intermittent Porphyria (AIP)

Question 14

(Acute symptoms only
Raised ALA in urine
PBG synthase deficiency
Rare)

Answer 14

ADA

Question 15

(Acute + blistering cutaneous symptoms
Raised C-III in urine
C-oxidase deficiency)

Answer 15

HCP

Question 16

(Acute + blistering cutaneous symptoms
Raised P-IX in urine
P-oxidase deficiency)

Answer 16

VP

Question 17

What is the most important Ix to do in an acute attack?

Answer 17

Collect urine, protect from light + measure haem pre-cursors to distinguish type
PBG is a good screen for whether it is porphyria!

Question 18

(Non-blistering cutaneous symptoms only
Children in China + Japan
Ferrochetelase deficiency)

Answer 18

EPP

Question 19

(Blistering cutaneous symptoms only
Myelodysplastic syndromes
U-III synthase deficiency)

Answer 19

CEP

Question 20

Blistering cutaneous symptoms only
Most common cutaneous
U-III decarboxylase deficiency
Triggered later in life by alcohol, hepatitis, cirrhosis

Answer 20

Porphyria cutanea tarda (PCT)

Question 21

Most common cutaneous

Answer 21

PCT

Question 22

Most common acute

Answer 22

AIP

Question 23

Acute attack Tx

Answer 23

Avoid precipitants
Pain relief
IV Haem arginate (replace Haem)

Question 24

Cutaneous Tx

Answer 24

Blood products
UV therapy
Avoid sun

Question 25

Main porphyrias to know

Answer 25

AIP (acute symptoms - HMB synthase deficiency - raised ALA + PBG - triggered by stress, OCP, alcohol, drugs) PCT (blistering cutaneous symptoms - U-III decarboxylase deficiency - triggered later in life)