The Porphyrias Flashcards
(22 cards)
What cause porphyria?
Genetic defects in any of the 7 enzymes of heme synthesis, leading to a buildup of pathway intermediates
What does the term “porphyria” mean?
Derived from Greek for red/purple, due to accumulation of coloured porphyrins
Is porphyria caused by lack of heme?
No, it is caused by accumulation of toxic intermediates, not anemia
How may genes are needed for heme synthesis?
Seven, one for each enzyme in the pathway
What determine the type of porphyria?
The specific enzyme defect and its position in the biosynthetic pathway
What are the two main types of porphyria symptoms?
Neurological and cutaneous (photosensitivity)
Name the 7 porphyrias
1 - ALAD
2 - AIP
3 - CEP
4 - PCT
5 - HCP
6 - VP
7 - EEP
What can trigger porphyria attacks?
Hormones, drugs, or dietary changes that increase pathway flux
What is the control point enzyme in heme synthesis?
5-Aminolevulininc acid synthase (ALAS)
Do ALAS mutations cause porphyria?
Usually no
They casue siderblastic anemia unless the mutation increases ALAS activity
What are symptoms of acute porphyria?
Abdominal pain
Vomiting
Neuropathy
Mental disturbance
What are symptoms of cutanous porphyria?
Skin blistering/lesions after sunlight exposure
Photophobia
What casues neurological symptoms in porphyria?
High levels of ALA, whuch may interfere with GABA neurotransmission
What causes cutaneous symptoms?
Accumulation of porphyrins that generate reactive oxygen species upon light exposure
What is the photodynamix effect in porphyria?
Porphyrins generate ROS when exposed to light and oxygen, damaging cells
How is prophyrin fluorescence used in medicine?
In photodynamic therapy for cancer: ALA or porphyrins are used to generate ROS under red light in metabolically active cells
How is porphyria managed?
Aviod triggers
Treat attacks with heme-arginate
Is there a cure for porphyria?
No, only management and avoidance of triggers
How are hereditary porphyrias typically inherited?
Autosomal dominant: only 2/7 are recessive
What does ‘partial penetrance’ mean in porphyria?
Not all individuals with a mutation show symptoms - 80% remain asymptomatic
What causes acquired porphyria?
Environmental toxins like hexachlorobenzene or lead, whic inactivate enzymes in the pathway
How does lead cause porphyria?
It displaces Zn2+ in ALA dehydratase, increasing ALA levels and mimicking porphyria
