Porphyria Flashcards
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)
What is EPP?
Photosensitivity only, no blisters
Only erythroid cells affected, therefore need to measure RBC protoporphyrin
What are acquired porphyrias?
•PCT most cases sporadic without family history
–Formation of specific inhibitor of uroporphyrinogen decarboxylase
- PCT-like syndrome hexachlorobenzene
- EPP and CEP a/w myelodysplastic syndromes
What is the diagnostic approach to porphyrias?
Q1: During acute porphyria, the most useful sample to send is…?
- Blood
- CSF
- Urine
- Muscle biopsy
- Stool
- Skin biopsy
Urine
Q2 Cutaneous erythema without blisters or bullae, most likely indicates…?
EPP
Q3: Hyponatraemia associated with AIP is due to….
SIADH
Q4 Urine samples taken during an acute attack for diagnosis should be…
- Taken in an acidified container
- Protected from light
- Alkalinised
- Interpreted with a paired serum sample
Protected from light
