Chemical Pathology 7 - Porphyrias Flashcards
What is haem?
Tetrapyrole rings surrounding a central iron
Roughly summarise the pathway of haem production
What is the rate limiting step?
1) ALA is generated in mitochondrion by ALA syntahse (THIS IS THE RATE LIMITING STEP)
2) ALA + ALA –> PBG
3) PBG –> HMB
4) HMB –> EITHER uroporphyriogen 1 or 3
5) Uroporphyrinogen 3 –> haem
By what 2 factors are porphyrias classified?
Acute/ non-acute
Neurovisceral or cutaneous
What is the cause of cutaneous symptoms in some porphyrias?
Porphyrin precursors build up under the skin and react with UV
**the reason this does not happen in cells is due to the low oxygen environment- but when they hit the skin there is more oxygen so they get oxidsied to porphyrins which then react with UV light to form active porphyrin**
porphyrin precursors–>porphyrin–>active porphyrin
Which toxic product leads to neurovisceral symptoms in porphyria?
5-ALA
What is the most common porphyria?
Porphyria cutanea tarda
**this is a chronic form**
What is the most common porphyria in children?
Erythropoietic protoporphyria
**again one of the non-acute ones**
What are the symptoms of ALA synthase deficiency?
Weirdly, doesn’t cause porphyria!
Instead, causes an X-linked sideroblastic anaemia
**this is because this is the first step in porphyrin synthesis, so you don’t get buildup of toxic products**
What are the 2 types of acute neurovisceral porphyria, which enzyme deficiency causes each, and how can they be clinically differentiated?
1) Acute intermittent porphyria (most common) = HMB synthase (or PBG deaminase) deficiency - causes ATTACKS
2) ALA dehydratase porphyria = PBG synthase deficiency - more one acute episode than numerous attacks
What are the symptoms of the acute neurovisceral porphyrias?
Motor neuropathy
Psychiatric symptoms
Severe abdominal pain
THINK Ps
i.e. painful abdomen, seizures, peripheral neuropathy, psychosis, Port urine, muscle weakness, constipation, urinary incontinence
*no cutaneous manifestations as no orphyrinogens*
What is the most likely cause of an acute intermittent porphyria ‘attack’?
Drug that is CYP450 inducer
other triggers: alcohol, oral contraceptive ppull, antibiotcis such as rifamoiciun and pyrazinamide**
How can acute porphyria be diagnosed?
Urine left in light changes colour
How should acute intermittent porphyria be managed?
Avoid attacks (adequate nutrition, precipitant drugs, prompt treatment)
IV carbs OR
IV haem arginate
Recall 2 forms of porphyria that have acute neurovisceral AND cutaneous symptoms
Hereditary coproporphyria
Variegate porphyria
Both autosomal dominant
Skin lesions on back of hands -> blistering under sun
Ix: Stool sample for coproporphyrinogen III
How do the cutaneous effects of porphyrias usually present and why?
Blistering on back of hands (most exposed to UV)
KMs book
