Chem path 8s - Porphyrias Flashcards
What is the first step in the haem biosynthesis pathway?
Succinyl CoA + glycine ā> 5-ALA (aminolaevulinic acid), catalysed by ALA synthase (rate-limiting step)
Which substrate is the main cause of neurotoxicity in porphyrias?
ALA is neurotoxic
Why are skin lesions seen in porphyrias?
Porphyrin precursors accumulate in skin which are oxidised and converted by UV light in to active porphyrins which are toxic
What is seen in the urine of someone with porphyria?
The urine will start off colourless/yellow and then turns red/yellow as the porphyrinogens are oxidised in to porphyrins
What is the most common type of porphyria?
Porphyria cutanea tarda
What is the most common porphyria in childrne?
Erythropoietic protoporphyria
What does ALA synthase deficiency cause?
Sideroblastic anaemia (not a porphyria)
Deficiency of which enzyme causes acute intermittent porphyria?
HMBS (porphobilinogen deaminase)
What does AIP lead to a rise of?
ALA and PBG
Inheritance pattern of AIP
Autosomal dominant
Presentation of AIP
90% are asymptomatic, certain triggers can result in an AIP attack.
4 Pās
- Painful abdomen
- Polyneuropathy
- Psych disturbances
- Port-wine urine
Neurovisceral attacks
- Hyponatraemia (SIADH) +/- seizures
- Tachycardia and hypertension
NO SKIN SYMPTOMS as no productino of porphryinogens
What are some precipitating factors of an AIP attack?
Most commonly seen in pre-menstrual women
ALA synthase inducers e.g. CYP450 inducing drugs, barbiturates, steroids, ethanol, anti-convulsants
Starvation
Stress
How is AIP diagnosed?
Urinary PBG and ALA levels
Diagnostic: erythrocyte hMBS activity
Treatment of AIP?
Avoid precipitating factors
High carb diet
IV Haem-arginate (turns off haem synthesis through -ve feedback)
Name two examples of acute porphyrias with skin lesions
Hereditary coproporphyria, variegate porphyria
What is hereditary coproporphyria due to?
Deficiency in coproporphyrinogen oxidase
What is variegate porphyria due to?
Deficiency in protoporphyrinogen oxidase
In acute porphyrias with skin lesions, why are the porphyrinogens detectable in the stool?
stool because the defect is towards the end of the pathway and, hence, the molecules are not as soluble (this is NOT seen in AIP)
Why do you get both neurovisceral and cutaneous presentation in acute porphyrias with skin lesions?
Because coproporphyrinogen III and protoporphyrinogen IX are potent inhibitors of HMBS which leads to build up of ALA and pBG
Where is the enzyme deficiency in erythropoietic protoporphyria (non-blistering, most common in paeds)
Ferrochetalase
Where is the enzyme deficiency in porphyria cutanea tarda?
Uroporphyrinogen III decarboxylase
What are the symptoms of PCT and its biochemistry?
Skin lesions, blistering
Raised urinary uroporphyrinogens
Raised ferritin
what is the management of pCT?
Avoid precipitants (alcohol, hepatic compromise), phlebotomy, hydroxychloroquine
What is the cardinal feature of erythropoietic protoporphyria?
Photosensitivity only with NO blisters! (as only RBCs are affected need to measure RBC protoporphyrin)
