C - Porphyrias (E) Flashcards
define porphyrias
deficiencies in enzymes of the haem biosynthestic pathway, leading to overproduction of toxic haem precursors
sx of porphyrias
acute neuro - visceral attacks
cutaenous - blistering or non blistering
what is the structure of haem
fe2+ in centre
4 pyrrolic rings around iron
what is cytochrome
electron transport chain component in mitochondria
which cells does haem synthesis affect
erythroid and liver cells
describe 1st step of haem biosynthesis and where it occurs
succinyl coA + glycine –> 5 ALA (ALA synthase)
mitchondria
what are the steps of haem biosynthesis that happen outside of mitochondria
ALA –> PBG (PBG synthase)
PBG –> HMB (HMB synthase)
HMB –> uroporphyrinogen I or III
uroporphyrinogen III –> coproporphyrinogen III
what is PBG
porphobilinogen
what is HMB
hydroxymethylbilane
what is HMB converted into
uroporphyrinogen I or II
how is it determined whether uroporphyrinogen I or II is made
I needs an ezyme, so if the enzyme isn’t present then II is made
what enzyme converts HMB to uroporphyrinogen III
uropoprphyrinogen III synthase
what are the 2 final steps of haem synthesis that take place in the mitochondria
coproporphyrinogen –> protoporphyrinogen IX –> protoporphyrin IX –> haem
what enzyme converts proptoporphyrin IX to haem
ferrochetalase
what enzyme converts coproporphyrinogen to protoporphyrinogen IX
coproporphyrinogen oxidase
what enzyme converts protoporphyrinogen IX to protoporphyrin IX
protoporphyrinogen oxidase
how can porphyrias be classified
erythroid / hepatic
acute / non acute
neurovisceral / skin lesions
what causes neurovisceral Sx
5 ALA build up - neurotoxic
what causes the skin lesions
activated porphyrins and O2
what are porphyrinogens
precurosor to porphyrins
how are porphyrinogens different to porphyrins
porphyrinogens are colourless and porphyrins are coloured
contrast stability of porphyrins vs porphyrinogens
porphyrinogens are unstable - readily oxidised
porphyrins are varied - near the start of pathway are stable, later on are not
which porphyrias are acute
ALA dehydratase
acute intermittent porphyria
hereditary coproporhyria
variegate porphyria
which porphyrias are non acute
congenital erythropoietic porphyria
porphyria cutanea tarda
erythropoietic protoporphyria
enzyme affected in acute intermittent porphyria
HMB synthase
enzyme affected in ALA dehydratase deficiency (PBG synthase deficiency)
PBG synthase
enzyme affected in hereditary coproporphyria
coproporphyrinogen oxidase
enzyme affected in variegate porphyria
protoporphyrinogen oxidase
enzyme affected in congential erythropoieitc porphyria
uroporphyrinogen III synthase
enzyme affected in porphyria cutanea tarda
uroporphyrinogen decarboxylase
enzyme affected in erythropoietic protoporphyria
ferrochetolase
most common porphyria
porphyria cutanea tarda (1/25,000)
which porphyria will you see in A&E
acute intermittent porphyria (1/100,000)
which prophyria is the most common one in kids
erythropoietic protoporphyria (EPP)
what does ALA synthase deficiency cause
NOT PORPHYRIA
x linked sideroblastic anaemia
is ALA dehydratase deficiency common
NO - very rare
what builds up in ALA drhydratase deficiiency
ALA but not PBG
precipitating factors that cause acute intermittent porphyrias
ALA synthase inducers - barbs, sterods, ethanol, antiuconvulsants
stress
reduced calroic intake
endocrine - premenstrual
Dx of AIP
increased urinary PBG
PBG gets oxidised so goes from yellow to purple
tx of AIP
avoid attacks
IV carbs - old Tx
IV haem arginate ** key Tx
how does haem arginate work as a Tx for AIP
porphyrias are part of haem synthesis pathway, so if you flood body w haem, the pathway gets turned off so toxic precursors not made
which porphyrias are both acute and cutaneous
hereditary coproporphyria
variegate porphyria
why do you get neurovisceral Sx in hereditary coproporphyria and variegate porphyria
the eynzymes that are affected inhibit HMB synthase which causes backing up so increase in PBG and increase in ALA –> ALA is neurotoxic so causes Sx
inheritance pattern of HCP
AD
Sx of HCP
acute neurovisceral attack
skin lesions / fragility - inc blisters, esp on back of hands
Sx of VP
skin lesions - blistering, on back of hands
neurovisceral Sx too
how can you differentiate between the acute porphyrias
AIP - no skin lesions
HCP and VP - skin lesions
urinary / faecal porphyrins - high in HCP/VP not AIP
best Ix for acute porphyrias
urine sample, protected from light
how do non acute porphyrias present
skin sx following sun exposure (hrs - days)
which non acute porphyria is non blistering
EPP - erythropoietic protoporphyria
EPP Sx
photosensitivity
burning
itching
oedema
–> all following sun exposure
what can cause acquired PCT
liver disease and drugs
how is EPP Ix and why
RBC protoporphyrin (blood test)
–> not a urine test as not detected there
what are EPP and CEP associated with
myelodysplastic syndromes
if acute features (neurovisceral) of ?porphyria, what Ix should you do
urine PBG (protected from light)
is the urine PBG is raised, what needs to be done next
enzyme activity
urine / faecal porphyrins
DNA
if skin features are present in ?porphyria, what Ix should you do
plasma / urine / faecal porphyrins
if the patient presents with photosensitivity in ?porphyria, what Ix should you do
red cell protoporphyrins
22F on holiday, drinking heavily. Presents to A&E
Abdo pain, nausea, vomitting, paranoia, tonic/clonic seizures, blurred vision and flashing lights. DDx?
porphyria - AIP
preg
