The heterogeneous group of diseases called the
porphyrias may all be characterised by derangement of specific stages in the
haem biosynthetic pathway. In the
acute porphyrias;
acute intermittent porphyria, urophorphyrinogen 1 synthase,
hereditary coproporphyria,
coproporphyrinogen oxidase and
variegate porphyria,
ferrochelatase or
protoporphyrinogen oxidase, are the
enzymes affected, whilst in the non
acute porphyrias, cutaneous
hepatic porphyria,
uroporphyrinogen decarboxylase, congenital
porphyria, uroporphyrinogen
cosynthase; and
erythropoietic protoporphyria;
ferrochelatase are the
enzymes affected. In each of the
porphyrias, the activity of the initial and rate controlling
enzyme of the pathway, delta-aminolaevulinic
acid synthase is raised which constitutes the principal control point of the pathway. Secondary control in each of these diseases lies at the leve of uroporphyrinogen 1 synthase. As a consequence of this secondary control, there is excessive excretion of the
porphyrin precursors delta-aminolaevulinic
acid and
porphobilinogen in the
acute porphyrias and excessive excretion of
porphyrins leading to solar photosensitivity in the non-
acute porphyrias and in variegate and
hereditary coproporphyria. There are a number of secondary metabolic aspects in the
porphyrias, such as the role of
steroid metabolism; the influence of drugs in the potentiation of attacks; and the potential for the pathway to branch at stages prior to
porphyrin formation which result in the synthesis of various monopyrroles. The
therapy of the two groups of
porphyrias are quite different. Prophylaxis is important in both types but is particularly important in the avoidance of various drugs in the
acute porphyrias. The acute attack may be specifically treated with
carbohydrates, beta-blockers and haematin. Cutaneous
hepatic porphyria may be treated by venesection,
erythropoietic protoporphyria with beta caratene whilst congenital
porphyria may be improved by
splenectomy and
chloroquine therapy.