Porphyria Flashcards
(32 cards)
What is a prophyria?
Deficiencies in enzymes of the haem biosynthetic pathway.
Deficiency of enzymes ranges from partial to complete.
What do porphyrias cause?
•Overproduction of toxic haem precursors
–Acute neuro-visceral attacks and/or
–Acute or chronic cutaneous symptoms.
What is Haem?
- Organic heterocyclic compounds
- Fe2+in centre
- 4 pyrrolic (tetrapyrrole) rings around the iron
- Carries oxygen
- Redox reactions
- Erythroid cells and liver cytochrome
- Made in all cells
Draw this out: (x5)
:)
Draw out the haem biosynthesis pathway x3
What may enzyme deficiencies do?
Build-up ALA, PBG or one of the -porphyrinogens
What can porphyrias be classed as?
Erythroid or hepatic
Acute or non acute
Neurovisceral or skin lesions
Why do acute/ neurovisceral S/S happen?
–5-aminolaevulinic acid is neurotoxic
Why do skin lesions happen?
Porphyrinogens
\/ oxidised
Porphyrins
\/ light
Activated porphyrins & O2
What is Porphyrinogens vs. porphyrins?
•Porphyrinogens are raised in porphyria
–Colourless compounds
–Unstable and readily oxidised to the corresponding porphyrin by the time urine /faeces reaches lab
•Porphyrins are highly coloured
–Porphyrins near start of the pathway are water soluble – urine (uro-)
–Porphyrins near end less soluble – faeces (copro-)
What are the types of porphyrias?
What is ALA synthase deficiency?
- Not a porphyria
- X-linked sideroblastic anaemia
What is PBG synthase deficiency?
- ‘ALA Dehydratase or Plumboporphyria’
- Extremely rare form of porphyria
- Build-up of ALA, but not PBG
- Diagnostic implications
What are the symptoms of HMB synthase deficiency?
Acute Intermittent Porphyria: Autosomal dominant
Neurovisceral attacks!
GI: Abdo pain, vomiting, constipation
Cardiovascular: Tachycardia, Hypertension, arrhythmias, cardiac arrest
Neurological: Seizures (hyponatraemia), sensory loss, weakness, psych symptoms
NO SKIN INVOLVEMENT BECAUSE NO PORPHYRINOGENS MADE!
What may cause symptomatic ‘attacks’ of acute intermittent porphyria?
Enzyme activity usually 50% of normal so 90% have no symptoms at all
Precipitating factors for attacks:
ALA synthase inducers: Barbiturates, steroids, ethanol, anticonvulsants
Stress: Infection, surgery
Reduced caloric intake
Endocrine factors: More common in women and premenstrual
How do you diagnose porphyria?
- Increased urinary PBG (and ALA)
- PBG gets oxidised to porphobilin
- Decreased HMBS activity in erythrocytes
How do you treat porphyria?
Conservative: Avoid attacks, Adequate nutritional intake, Avoid precipitant drugs, Prompt treatment infection/illness
Medical: iv carbohydrate, iv haem arginate
What are the •Acute porphyrias with skin lesions?
Hereditary coproporphyria
Variegate porphyria
What does Coproporphyrinogen oxidase cause?
•Hereditary Coproporphyria (HCP)
–Autodomal dominant
–Acute neurovisceral attack
–Skin lesions
- Blistering
- Skin fragility
What is Variegate Porphyria (VP)?
•Variegate Porphyria (VP)
–Autosomal dominant
–Acute attacks
–Skin lesions
How can we differentiate the acute porhyrias?
- AIP – no skin lesions
- HCP & VP – skin lesions
- Urine PBG – raised in all three
- Urine and faeces for porphyrins
–Raised HCP or VP, but not AIP
- Enzyme activity variable
- DNA definitive but large number of mutations
What are Non-Acute porphyrias?
- Only present with skin lesions
- No neuro-visceral manifestations
What are the types of non acute porphyrias?
- Congenital Erythopoietic porphyria
- Porphyria Cutanea Tarda
- Erythropoietic protoporphyria
- Skin affected only e.g. blisters, fagility, pigmentation, erosions etc. delay following sun exposure
- EPP: photosensitivity, burning, itching oedema following sun exposure
What is PCT?
- Inherited or acquired
- Uroporphyrinogen decarboxylase deficiency
- Formation of vesicles on sun-exposed areas of skin crusting, superficial scarring, pigmentation
Biochemistry:
- Urinary (& plasma) uroporphyrins & coproporphyrins increased
- Ferritin often increased
- Avoid precipitants (alcohol, hepatic compromise)
