Chempath 8: Porphyrias

Question 1

Porphyrias are caused by enzyme deficiency in the …………. synthesis pathway

Answer 1

Haem

Question 2

acute intermittent porphyria (AIP) presents with ………… but not …………..

Answer 2

Neurovisceral signs

Skin lesions

Question 3

hereditary corporphyria (HCP) and variegate porphyria (VP) present with ………. and ……………

Answer 3

Neurovisceral signs

Skin lesions

Question 4

congenital (CEP) erythropoietic protoporphyria (EPP) and porphyria cutanea trade (PCT) are the 3 non acute porphyria and present with …………. only.

Answer 4

Skin lesions

Question 5

List some Skin lesions seen in porphyrias?

Answer 5

Blisters
skin fragility
pigmentation

Question 6

choose the most common porhyria out of this list ?

A) CEP
B) EPP
C) PCT
D) HCP
E) VP
F) AIP

Answer 6

PCT

Porphyria cutanea tarda is the most common porphyria most likely because it can be acquired sporadically It presents with skin lesions

Question 7

Which non-acute porphyria presents with skin lesions which are photosensitive and without blisters ?

Answer 7

EPP

Erythropoietic protoporphyria is a non-acute porphyria which means it only has skin lesions and no neurovisceral signs. This non-acute porphyria does not have blisters

Question 8

Why do HCP and VP have both skin lesions and neurovisceral lesions?

Answer 8

HCP - hereditary corporphyria is caused by deficiency in corporphyrinogen oxidase. This causes excess Uroporphyrinogen 3 oxidase which causes skin lesions if exposed to UV light. Uroporphyrinogen 3 oxidase also has negative feedback on HMB synthase which causes build up of PBG. PBG causes neurovisceral lesions.

VP is similar but different enzyme deficiency.

Question 9

List 3 ALA synthase inducers which can trigger AIP ?

Answer 9

• Steroids
• Alcohol
• COCP

Question 10

How is AIP inherited ?

Answer 10

Autosomal dominant

Question 11

Which disease is caused by a mutation in the gene encoding ALA synthase ?

Answer 11

X-linked sideroblastic anaemia

Question 12

List 4 symptoms of AIP ?

Answer 12

4 Ps

Psychological disturbance
Painful abodmen
polyneuropathy
Port wine coloured urine (porphobilinogen oxidises in light and turns a wine colour)

Only neuro-visceral symptoms

Question 13

what are porphyrias

Answer 13

7 disorders cause by deficiency in enzymes involved in heme biosynthesis, leading to build up of toxic heme products which manifests

acute neuro-visceral attacks
acute or chronic cutaneous symptoms

Question 14

what key enzymes are involved in heme synthesis

Answer 14

ALA synthase
PBG synthase
HMB synthase…

Question 15

describe the mechanism of neurovisceral symptoms

Answer 15

5 -ALA is neurotoxic

Question 16

describe the mechanisms of skin lesions

Answer 16

prophyrinogens –> porphyrins –> activated porphyrins + 02
uv light converts to active porphyrins
porphyrinogens raised in porphyria
porphyrins are highly coloured - colourless/yellow urine turns red/dark red/deep purple

Question 17

list types of porphyrias

Answer 17

acute:

• ALA dehydrates
• acute intermittent porphyria
• hereditary coproporphyria
• variegate porphyria

non-acute:

• congenital eryhropoietic porphyria
• porphyria cutanea tarda
• erythorpoietic protoporphyria

Question 18

most common type or porphyria

Answer 18

porphyria cutanea tarda

Question 19

most common porphyria in children

Answer 19

erythropoietic photoporphyria

Question 20

features of ALA synthase deficiency

Answer 20

does not cause any porphyrias
causes x-linked sideroblastic anaemia
build-up of protoporphyrin IX

Question 21

features of PBG synthase/ ALA dehydratase deficiency (acute porphyria)

Answer 21

accumulation of ALA
rare
neurological symptoms
presents with ABDOMINAL PAIN

Question 22

features of acute intermittent porphyria

Answer 22

HMB synthase deficiency
AD inheritance
rise in PBG and ALA
neurovisceral attacks: abdo pain, seizures, psych disturbance, nausea and vomiting, tachycardia, hypertension, sensory loss, muscle weakness, constipation, urinary incontinence
no cutaneous manifestations (absence of porphyrinogens)
only 10% have symptoms
diagnosis: ALA and PBG in urine (port wine urine)
precipitating factors: ALA synthase inducers (steroids, alcohol, barbs)
stress
reduced calorie intake and endocrine factors
treatment: avoid precipitating factors, analgesia, IV CARBS/HAEM ARGINATE

Question 23

features of acute porphyrias with skin lesions

Answer 23

hereditary coproporphyria (HCP, deficiency of coproporphyrinogen oxidase) and variegate porphyria (VP - deficiency of protoporphyrinogen oxidase)

both have detonable levels of porphyrinogens in the stool as the defect is towards the end of the pathway so molecules are not as soluble

both are inhibitors of HMB synthase
accumulation of PBG and ALA

Question 24

features of non acute porphyrias

Answer 24

only presents with skin lesions

congenital erythropoietic porphyria (CEP) - uroporphyrin III synthase
erythropoietic protoporphyria (EPP) - ferrochetelase
porphyria cutanea tarda (PCT) - uroporphyrinogen decarboxylase

blisters, fragility, pigmentation, erosions

hours to days after sun exposure

Question 25

features of EPP

Answer 25

photosensitivity, burning, itching oedema following sun exposure

non-blistering

treat with sun avoidance

Question 26

features of PCT

Answer 26

inherited/acquired
uroporphyrinogen decarboxylase deficiency
formation of vesicles on sun-exposed skin (crusting, pigmented, superficial scarring)
diagnosis: high urinary uroporphyrins + coproporphyrins + high farritin
treatment: avoid precipitation its (alcohol, hepatic compromise)