Chempath 8: Porphyrias Flashcards
Porphyrias are caused by enzyme deficiency in the …………. synthesis pathway
Haem
acute intermittent porphyria (AIP) presents with ………… but not …………..
Neurovisceral signs
Skin lesions
hereditary corporphyria (HCP) and variegate porphyria (VP) present with ………. and ……………
Neurovisceral signs
Skin lesions
congenital (CEP) erythropoietic protoporphyria (EPP) and porphyria cutanea trade (PCT) are the 3 non acute porphyria and present with …………. only.
Skin lesions
List some Skin lesions seen in porphyrias?
Blisters
skin fragility
pigmentation
choose the most common porhyria out of this list ?
A) CEP B) EPP C) PCT D) HCP E) VP F) AIP
PCT
Porphyria cutanea tarda is the most common porphyria most likely because it can be acquired sporadically It presents with skin lesions
Which non-acute porphyria presents with skin lesions which are photosensitive and without blisters ?
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
Why do HCP and VP have both skin lesions and neurovisceral lesions?
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.
List 3 ALA synthase inducers which can trigger AIP ?
- Steroids
- Alcohol
- COCP
How is AIP inherited ?
Autosomal dominant
Which disease is caused by a mutation in the gene encoding ALA synthase ?
X-linked sideroblastic anaemia
List 4 symptoms of AIP ?
4 Ps
Psychological disturbance
Painful abodmen
polyneuropathy
Port wine coloured urine (porphobilinogen oxidises in light and turns a wine colour)
Only neuro-visceral symptoms
what are porphyrias
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
what key enzymes are involved in heme synthesis
ALA synthase
PBG synthase
HMB synthase…
describe the mechanism of neurovisceral symptoms
5 -ALA is neurotoxic
describe the mechanisms of skin lesions
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
list types of porphyrias
acute:
- ALA dehydrates
- acute intermittent porphyria
- hereditary coproporphyria
- variegate porphyria
non-acute:
- congenital eryhropoietic porphyria
- porphyria cutanea tarda
- erythorpoietic protoporphyria
most common type or porphyria
porphyria cutanea tarda
most common porphyria in children
erythropoietic photoporphyria
features of ALA synthase deficiency
does not cause any porphyrias
causes x-linked sideroblastic anaemia
build-up of protoporphyrin IX
features of PBG synthase/ ALA dehydratase deficiency (acute porphyria)
accumulation of ALA
rare
neurological symptoms
presents with ABDOMINAL PAIN
features of acute intermittent porphyria
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
features of acute porphyrias with skin lesions
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
features of non acute porphyrias
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
features of EPP
photosensitivity, burning, itching oedema following sun exposure
non-blistering
treat with sun avoidance
features of PCT
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)
