Porphyrias

Question 1

What are porphyrias?

Answer 1

7 disorders caused by def of any enzyme in the heme biosynthesis pathway which leads to build up of toxic heme precursors.

they are classified based on acute or non acute

neurovisceral or skin lesions.

Question 2

If experiencing an acute or neurovisceral attack it is ALWAYS due to a build up of what heme precursor?

Skin lesions are due to an accumulation of what?

Answer 2

ALA (is neurotoxic)

Porphyrinogens

Question 3

AIP:

• which enzyme is def?
• give 3 features

Answer 3

• due to HMB synthase def
• features
  
  • classic exam case will be Psych problems + recurrent abdo pain
  • abdo pain + vom
  • hyponatremia +/- seizures (thought to cause SIADH)
  • muscle weakness + psych symp
  • life threatening arrythmias / cardiac arrest

Question 4

AIP:

• precipitating factors (3)
• Dx (1)

Answer 4

1. ALA synthase inducers - steroids, barbituates. alcohol, anticonvulsants
2. stress - surgery, infection
3. starvation
4. endocrine factors- women + premenstrual

NB - 90% of ppl with AIP have no symp (because still have 50% enzyme activity)

Dx - increased urinary PBG (also ALA)

Question 5

Management of AIP (3)

Answer 5

• avoid precipitants
• adequate nutrition, prompt treatment of infection etc.
• IV carb
• IV haem arginate

Question 6

There are 2 porphyrias that cause both neurocutaneous & skin lesions = acute porphyrias. As said before acute porphyrias always due to ALA build up.

What are they? (2)

Answer 6

1. HCP - hereditary coproporphyria (def in coprophryinogen oxidase)
2. Variegate porphyria (VP) (def in protoporphyrin oxidase)

(the build of the substrates these enzymes act on in addition to causing a build up of porphyrinogens also inhibit HMB synthase - there by causing ALA build up and acute/neurovisceral features)

So they also cause skin blistering and fragility

Question 7

How to differentiate the acute porphyrias?

Answer 7

• whenever see acute features 1st thing URINE PBG - raised in all 3
• urine & faeces for porphyrins - only rasied in HCP & VP

Question 8

Non-acute porphyrias: name the 3

Answer 8

1. porphyria cutanea tarda (most common) (PCT)
2. congenital erythropoeitc porphyria (CEP)
3. erythropoietic protoporphyria (EPP)

Question 9

CPP & ECT have similar symptoms - only skin affected.

How is EPP different? (2 features)

Answer 9

•Skin affected only e.g. blisters, fagility, pigmentation, erosions etc. delay following sun exposure

EPP doesnt get any skin blistering or fragility - only photosensitivity, burning, itching oedema following sun exposure. only erythoid cells affected (last step in pathway) - so need to measure RBC protoporphyrin

Question 10

Picture of diagnostic approach

Answer 10

Acute features > urine PBG

• if normal excludes attack
• if raised > urine/ faeces porphyrins
  
  • can also do enzyme activity/ DNA

Skin features > urine / faecal porphyrins

photosensitivity > RBC protoporphyrins (suspected EPP)