Biochemical and Clinical Transitions Between the Hereditary Hepatic Porphyrias: New Concepts
Acute hepatic porphyrias are primarily molecular regulation diseases that are based on disturbances in porphyrin and heme biosynthesis (Fig. 1). Between the acute hepatic porphyrias — namely acute intermittent porphyria (AIP), porphyria variegata (PV), and hereditary coproporphyria (HCP) — there is an uninterrupted biochemical transition. Acute hepatic porphyrias have a series of common features, especially the sensitivity to lipid-soluble drugs, premenstrual manifestation, clinical syndrome with abdominal, cardiovascular, nervous and psychic symptoms, a similar constellation in the high urinary excretion of porphyrin precursors and porphyrins, and increased porphyrin excretion in feces in PV, in HCP, and in AIP. There is increased inducibility of 6-aminolevulinic acid (ALA) synthase in the Liver as a consequence of partial enzyme defects along the synthesis chain, of uroporphyrinogen synthase (uro-S) in AIP, of coproporphyrinogen oxidase in HCP, and probably of ferrochelatase or protoporphyrinogen oxidase in PV (Table 1). All respond to glucose, propranolol, and hematin therapy. They generally follow four phases: the phase of the genetic defect, the compensated and decompensated latent phase, and the clinical manifestation. From the clinical and biochemical point of view one can differentiate between a compensated and an uncompensated latent phase both in AIP and in PV (Table 2). AIP, PV, and HCP can appear with a syndrome clinically identical. In half of the cases of variegata we observed no skin symptoms.
KeywordsAcute Intermittent Porphyria High Urinary Excretion Hepatic Porphyria Variegate Porphyria Protoporphyrinogen Oxidase
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