Porphyrias Flashcards
What is a porphyria?
Disorder caused by deficiency in an enzyme of haem synthesis
What does this lead to and how can it manifest itself?
Build up of toxic haem precursors
Manifest as:
- Acute neuro-visceral attacks
- Acute or chronic cutaneous symptoms
What is the structure of haem?
Organic heterocyclic compound
Fe2+ in the centre
4 pyrrolic rings around the iron
Carries oxygen
Where does haem synthesis begin?
In the mitochondrion
Where is ALA generated?
In the mitochondrion
What converts ALA to PBG?
PBG synthase
What converts PBG to HMB?
HMB synthase
What is required for HMB to be converted to uroporphyrinogen 2?
Uroporphyrinogen 3 synthase
If uroporphyrinogen 3 is not present, what is HMB converted to?
Uroporphyrinogen 1
What enzyme converts Uroporphyrinogen 3 to coproporphyrinogen 3?
Uroporphyrinogen decarboxylase
Where does coproporphyrinogen 3 go after it has been produced?
Back into the mitochondrion
What converts coproporphyrinogen 3 to protoporphyrinogen 9?
Coproporphyrinogen oxidase
What converts protoporphyrinogen 9 to protoporphyrin 9?
Protoporphyrinogen oxidase
What is protoporphyrin 9?
Haem without the iron
Which enzyme converts protoporphyrin 9 to haem?
Ferrochetalase
Where can the enzyme deficiencies be (in the body)?
Erythroid
Hepatic
What is the most common type of porphyria?
Porphyria cutanea tarda
What is the most common type of porphyria in children?
Erythropoietic protoporphyria
What does ALA synthase deficiency show on a blood film?
Sideroblasts
X-linked sideroblastic anaemia
Which enzyme is deficient in acute porphyria?
PGB synthase
Leads to accumulation of ALA
Very rare
Neurological symptoms + abdominal pain
Which enzyme is deficient in acute intermittent porphyria?
HMB synthase
Autosomal dominant
Neurovisceral attacks
No skin symptoms
What can precipitae acute intermittent porphyria?
ALA synthase inducers (barbiturates, steroids, ethanol, anticonvulsants)
Stress
Reduced caloric intake
Endocrine factors
How are attacks of acute intermittent porphyria treated?
IV carbohydrate (inhibits ALA synthase) IV haem arginate (turns off haem synthesis through negative feedback)
Which two acute porphyrias also have skin manifestations?
Hereditary coproporphyria
Variegate porphyria
Where does blistering typically occur in hereditary coproporphyria?
Backs of hands
Appear hours/days after sun exposure
What happens to the urine PBG in all types of acute porphyria?
Raised
What do the urine and faeces porphyrin levels look like in the 3 types of acute porphyrias?
HCP + VP = high
AIP = not high
What do non-acute porphyrias present with?
Skin lesions
No neurovisceral manifestations
What tends to bring on the skin lesions in non-acute porphyrias?
Sun exposure
Which non-acute porphyria is NON-BLISTERING?
Erythropoietic protoporphyria
Tends to present with photosensitivity, burning, itching and oedema after sun exposure
What is the triad of symptoms of acute porphyrias?
Abdominal pain
Neurological symptoms
Psychiatric symptoms
During acute porphyria, what is the most useful sample to send?
Urine (PBG)
