Porphyrias Flashcards
What is a porphyria
Disorder caused by deficiency in enzymes of haem synthesis pathway
What does porphyria lead to an overproduction of?
Overproduction of toxic haem precursors
Which two possible ways does porphyria present ?
ACUTE Neuro-visceral attacks
CHRONIC cutaneous symptoms
What are the principal sites of enzyme deficiency?
Erythroid
Hepatic
What are neurovisceral symptoms due to?
Accumulation of 5-ALA
5-ALA is NEUROTOXIC
What are skin lesions due to?
Due to accumulation of PORPHYRINS
How do skin lesions get caused by light?
Porphyrins accumulate in skin
Porphorins are oxidised and converted by UV light to active porphyrins, which are toxic
What colour are porphyrins?
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
What is the most common porphyria?
porphyria cutanea tarda
What is the most common porphyria in children?
Erythropoetic protoporphyria
What does ALA synthase deficiency cause?
X LINKED SIDEROBLASTIC ANAEMIA
not any porphyria
What is the key clinical feature of PBG synthase deficiency?
abdominal pain
What is the inheritance method for acute intermittent porphyria?
Autosomal DOMINANT
What are features of Acute Intermittent Porphyria?
Neurovisceral attacks:
- abdo pain, vomiting
- high BP, HR
- constipation, urinary incontinence-
- hyponatraemia, seizures
- psychological symptoms
- arrythmia, cardiac arrest
What is tx for Acute Intermittent Porphyria
Avoid attacks (adequate nutritional intake, avoid drugs) IV carbohydrate (inhibit ALA synthase) IV haem arginate
What are the TWO acute porphyrias that present with skin lesions?
Hereditary coproporphyria
Variegate porphyria
What is the blistering type of chronic porphyria?
Porphyria cutanea tarda (PCT)
What are clinical presentations of porphyria cutanea tarda?
Vescicles on sun-exposed areas
skin crusting
superficial scarring
pigmentation
What are clinical presentations of Erythropoietic Protoporphyria?
photosensitivity burning itching oedema occurs minutes after sun exposure
What chemical triggers acquired porphyrias?
Hexachlorobenzene
during an acute porphyria, what is the most useful sample to send=?
urine
What is urine PGB like in acute porphyrias
Raised urine PGB in ALL THREE (AIP, HCP, VP)
what are porphorins like in urine and faeces of acute porpyrias
HIGH in HCP, VP
LOW in AIP (because too soluble, doesn’t enter faecews)
What does urine test for erythropoetic protoporphyria show
NOTHING - as protoporphorin is at end of pathway so not solube
HOw can you detect erythropoetic protoporphyria
RBC protoporphorin
How do you confirm porphyria cutanea taarda
Urine / plasma uroporphyrins, coproporphyrins
What must you send off if photosensitivity and syspecting a porphyria
Red cell protoporphyrins
what are precipitating factors of acute intermittent porphyria
Drugs (ALA synthase inducers): barbituates, steroids, ethanol, anticonvulsants
Stress (infection, surgery)
Reduced caloric illness (esp carbohydrtes)
Endocrine (in women, pre-menstrul)
