Porphyrias

Question 1

What is a porphyria

Answer 1

Disorder caused by deficiency in enzymes of haem synthesis pathway

Question 2

What does porphyria lead to an overproduction of?

Answer 2

Overproduction of toxic haem precursors

Question 3

Which two possible ways does porphyria present ?

Answer 3

ACUTE Neuro-visceral attacks

CHRONIC cutaneous symptoms

Question 4

What are the principal sites of enzyme deficiency?

Answer 4

Erythroid

Hepatic

Question 5

What are neurovisceral symptoms due to?

Answer 5

Accumulation of 5-ALA

5-ALA is NEUROTOXIC

Question 6

What are skin lesions due to?

Answer 6

Due to accumulation of PORPHYRINS

Question 7

How do skin lesions get caused by light?

Answer 7

Porphyrins accumulate in skin

Porphorins are oxidised and converted by UV light to active porphyrins, which are toxic

Question 8

What colour are porphyrins?

Answer 8

Those near the start of the pathway are WATER SOLUBLE - they are excreted in urine and turn it purple

Those at end of pathway are less soluble - excreted in faeces

Question 9

What is the most common porphyria?

Answer 9

porphyria cutanea tarda

Question 10

What is the most common porphyria in children?

Answer 10

Erythropoetic protoporphyria

Question 11

What does ALA synthase deficiency cause?

Answer 11

X LINKED SIDEROBLASTIC ANAEMIA

not any porphyria

Question 12

What is the key clinical feature of PBG synthase deficiency?

Answer 12

abdominal pain

Question 13

What is the inheritance method for acute intermittent porphyria?

Answer 13

Autosomal DOMINANT

Question 14

What are features of Acute Intermittent Porphyria?

Answer 14

Neurovisceral attacks:

• abdo pain, vomiting
• high BP, HR
• constipation, urinary incontinence-
• hyponatraemia, seizures
• psychological symptoms
• arrythmia, cardiac arrest

Question 15

What is tx for Acute Intermittent Porphyria

Answer 15

Avoid attacks (adequate nutritional intake, avoid drugs) 
IV carbohydrate (inhibit ALA synthase) 
IV haem arginate

Question 16

What are the TWO acute porphyrias that present with skin lesions?

Answer 16

Hereditary coproporphyria

Variegate porphyria

Question 17

What is the blistering type of chronic porphyria?

Answer 17

Porphyria cutanea tarda (PCT)

Question 18

What are clinical presentations of porphyria cutanea tarda?

Answer 18

Vescicles on sun-exposed areas
skin crusting
superficial scarring
pigmentation

Question 19

What are clinical presentations of Erythropoietic Protoporphyria?

Answer 19

photosensitivity 
burning 
itching 
oedema 
occurs minutes after sun exposure

Question 20

What chemical triggers acquired porphyrias?

Answer 20

Hexachlorobenzene

Question 21

during an acute porphyria, what is the most useful sample to send=?

Answer 21

urine

Question 22

What is urine PGB like in acute porphyrias

Answer 22

Raised urine PGB in ALL THREE (AIP, HCP, VP)

Question 23

what are porphorins like in urine and faeces of acute porpyrias

Answer 23

HIGH in HCP, VP

LOW in AIP (because too soluble, doesn’t enter faecews)

Question 24

What does urine test for erythropoetic protoporphyria show

Answer 24

NOTHING - as protoporphorin is at end of pathway so not solube

Question 25

HOw can you detect erythropoetic protoporphyria

Answer 25

RBC protoporphorin

Question 26

How do you confirm porphyria cutanea taarda

Answer 26

Urine / plasma uroporphyrins, coproporphyrins

Question 27

What must you send off if photosensitivity and syspecting a porphyria

Answer 27

Red cell protoporphyrins

Question 28

what are precipitating factors of acute intermittent porphyria

Answer 28

Drugs (ALA synthase inducers): barbituates, steroids, ethanol, anticonvulsants

Stress (infection, surgery)

Reduced caloric illness (esp carbohydrtes)

Endocrine (in women, pre-menstrul)