Chem Path - porphyrias

Question 1

Most common

Answer 1

Porphyria cutanea tarda

Question 2

Most common in children

Answer 2

Erythropoietic protoporphyria

Question 3

2nd most common and acute

Answer 3

Acute intermittent porphyria

Question 4

Neuravisceral symptoms are due to what

Answer 4

↑ALA (5-aminolaevulinic acid)

Question 5

Cutaneous symptoms are due to what

Answer 5

Porphyrinogens in the blood and oxidising (by sunlight) to become porphyrins. These oxidised phorphyrins then cause mast cell degranulation (leading to cutaneous symptoms)

Question 6

Porphyrinogen vs Porphyrins colour

Answer 6

Porphyrinogens - colourless

Porphyrins - Purple or dark red

Question 7

Acute Intermittent Porphyria

Which enzyme is deficient?

Answer 7

HMB Synthase

It is about 50% deficient, therefore a triggering factor, which would cause oxidative stress and inhibit HMB synthase, may be enough to give someone an ‘attack’ due to ↑ALA.

Question 8

AIP

What test to diagnose?

Answer 8

Urine Sample

There should be ALA and PBG in the urine “port wine urine” - should be dark red/purple due to how easily PBG gets oxidised.

Question 9

AIP

What are the precipitating factors?

Answer 9

Anything that would ↑Oxidative stress

ALA Synthase inducers - these are generally CyP450 inducers - steroids, alcohol, barbituates, phenytoin

Stress - infection, surgery

Reduced calorie intake - carbohydrates are an inhibtor of the haem synth pathway so ↓Carbs means ↑haem synth which can trigger an attack

Endocrine factors - more common in women

Question 10

AIP

Rx?

Answer 10

Haem arginine - inhibitor of haem synth pathway due to negative feedback effect

Carbs - same reason as above

Correct electrolyte - AIP often causes SIADH and hyponatraemia

Avoid risk factors

Question 11

Pt presents with an attack which you suspect to be an acute porphyria, so you check their urine. There urine contains a lot of ALA but nothing else of note.

Answer 11

ALA Dehydratase Porphyria

Extremely rare - only 10 cases ever reported. Can present in childhood or adulthood. Autosomal recessive

Question 12

Pt presents with acute porphyria attack but also has cutaneous symptoms as well. Urine sample shows ↑porphobillinogen (PBG). Which 2 diseases could this be?

Answer 12

Hereditary Coproporphyria OR Variegate Porphyria

Both are ‘acute cutaneous’, meaning they produce both the acute and cutaneous symptoms of porphyrias. This is due to coproporphyrinogen and protoporphyrinogen being inhibitors of HMB synthase.

HC is caused by deficiency in Coproporphyrinogen oxidase and VP is caused by Protoporphyrinogen oxidase

To further differentiate, extensive stool sampling would be ideal. In HC, there would be ↑Coproporphyrinogen and in VP, there would be ↑Protoporphyrinogen

Question 13

Adult Pt presents with cutaneous symptoms.

Answer 13

Porphyria cutanea tarda

Deficiency in uroporphyrinogen decarboxylase. ↑Uroporphyrins and ↑Coproporphyrins on urine, stool and microscopy. ↑Ferritin is also common.

Associated with long term alcoholism - causes ↓hepcidin, causing increased iron absorption and ↓oxidative stress as well as stimulating haem pathway. Also associated with Hep C

Rx: avoid sunlight and precip factors

Question 14

Neonate Pt presents with cutaneous symptoms.

Answer 14

Congenital erythropoietic porphyria

Aka gunther disease. Deficiency in Uroporphyrinogen III synthase. Very rare.

Question 15

Child presents with photosensitivity but no cutaneous symptoms.

Answer 15

Erythropoietic protoporphyria

Deficiency in ferrochelotase. This step in pathway only happens in erythroid cells - so we want to measure RBC protoporphyrin IX. No blisters.