Porphyrias

Defect in the enzymes of haem synthesis

7 types; 5 liver, 2 erythroid

Classified by whether the predominantly affected organ is the liver or erythron

Erythroid porphyries

Congenital erythropoietic porphyria

• Autosomal recessive – very rare
• Photosensitive skin lesions which can be very disfiguring
• Haemolytic anaemia
• Splenomegaly

Treatment

• Avoidance of sunlight
• Splenectomy to improve haemolysis
• High level blood transfusion to suppress erythropoiesis (combined with iron chelation) have been used to reduce pophyrin production to abolish clinical symptoms
• Allogenic BMT

Eythropoietic porphyria

• AD – more common
• Ferrochelatase deficiency
• Leads to increased protoporphyrin in bone marrow, red cells and bile
• Variable clinical picture
• Photosensitivity and dermatitis
• Mild hypochromic anaemia with little haemolysis
• Accumulation of protoporphyrins can occasionally lead to severe liver disease
• Iron deficiency should be avoided

Acute porphyries

All except erythroid and PCT

Clinical features

• Abdominal pain. Vomiting, diarrhoea
• Pain, behavioural change, paralysis
• Tachycardia and hypertension

• Triggered by increased demand for hepatic haem (particularly the cytochrome P450 enzymes)
• Alcohol, barbiturates, carbamazepine, phenytoin, rifampicin, sulphonamides
• Cigarette smoking
• Metabolic stress and surgery

Diagnosis

• All porphyrias have a rise in urine porphyrobilinogen (apart from ALA, the first enzyme in the pathway in which ALA is increased and erythopoietic protoporphyrin, the last enzyme in the pathway where protoporphyrin is increased)

Treatment

• Glucose – inhibits hepatic ALA synthetase
• Hemin – suppresses hepatic ALA synthetase activity
• Can return the porphyrobilinogen and other intermediate levels to normal very quickly