Porphyrias Flashcards
What is porphyria?
Deficiency (partial/complete) of enzymes in haem biosynthesis –>
Overproduction of toxic haem precursors
How do we classify porphyria’s?
Principal site of enzyme deficiency
o Erythroid or hepatic
Clinical presentation
o Acute or non-acute
o Neurovisceral or skin lesions
Not perfect, there are overlaps
What are 3 clinical presentations of porphyria’s?
- Neurovisceral symptoms
- Blistering cutaneous symptoms
- Non-blistering cutaneous symptoms
What causes neurovisceral symptoms in porphyria’s?
Accumulation of 5-ALA which is neurotoxic
What causes cutaneous symptoms in porphyria’s?
Porphyrin pre-cursors accumulate in the skin
Pre-cursors are oxidised by UV light
Become toxic
What is the difference between porphyrinogens and porphyrins?
Porphyrinogens are pre-cursors to porphyrins
*Porphyrinogens are RAISED in porphyria (colourless and unstable), will oxidise quickly and become coloured
- Porphyrins are HIGHLY COLOURED (water soluble at start of chain, less soluble at end)
What is the porphyria caused by PBG synthase?
ALA Dehydratase / Plumboporphyria
What is the porphyria caused by HMB synthase?
Acute intermittent porphria
What enzyme causes hereditary coproporphyria?
Coproporphyrinogen oxidase
What enzyme causes variegate porphyria?
Protoporphyrionogen oxidase
What are the acute porphyrias?
ALA Dehydratase / Plumboporphyria
Acute intermittent porphria
Hereditary Coproporphyria
Variegate porphyria
What are the non-acute porphyrias?
Congential erythropoietic porphria
Porphyria cutanea tarda
Erythropoietic protoporphria
What enzyme causes Congential erythropoietic porphria?
Uroporphyrinogen III synthase?
What enzyme causes Porphyria cutanea tarda?
Uroporphyrinogen decarboxylase
What enzyme causes Erythropoietic protoporphria?
Ferrochetolase
What is the most common porhyria?
Porphyria cutanea tarda
What is the most common porphyria in children?
Erythropoietic protoporphyria
What is ALA synthase deficiency?
NOT at porphyria
X-linked sideroblastic anaemia
What happens in Acute Porphyria / Plumboporphyria?
Accumulation of ALA
Lack of PBG
What are the symptoms of Acute Porphyria / Plumboporphyria?
Neurological (e.g. coma, bulbar palsy, motor neuropathy)
Abdominal pain (most important feature)
+/- psychiatric symptoms
What happens in Acute Intermittent Porphyria?
HMB Synthase Deficiency
PBG goes up
ALA goes up
What are the clinical signs for AIP?
No cutaneous symptoms
Neurovisceral:
Abdominal pain and vomiting
Tachycardia and hypertension
Constipation, urinary incontinence
Hyponatraemia (SIADH) ± seizures
Psychological symptoms
Sensory loss/muscle weakness
Arrhythmias/cardiac arrest
What are precipitating factors for AIP?
ALA synthase inducers – barbiturates, steroids, ethanol, anti-convulsants
Stress – infection, surgery
Reduced caloric intake
Endocrine factors – F>M, pre-menstrual
How do you diagnose AIP?
Urine sample - protect from light and get to lab, will turn purple in light
