SUMMARY Autonomic function was assessed in subjects with acute intermittent porphyria and age-and sex-matched controls using five different bedside tests of cardiovascular reflexes. During the acute attack both parasympathetic and sympathetic tests were impaired, but subsequently improved during remission. Early parasympathetic dysfunction was also detected during remission and in latent asymptomatic acute intermittent porphyria.Acute intermittent porphyria is an autosomal dominant inborn error of metabolism characterised by a partial deficiency in the activity of the haem biosynthetic enzyme, porphobilinogen deaminase (PBG). Consequently the porphyrin precursors delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG) accumulate in blood and are excreted in excessive amounts in the urine.' 2The clinical manifestations of acute intermittent porphyria have been attributed to a widespread neurological dysfunction caused by the block in haem biosynthesis.34 Abdominal pain is the commonest and often the most troublesome symptom which occurs in more than 90% of cases.5 It has been explained on the basis of splanchnic autonomic dysfunction, thus providing a mechanism for the intestinal dilatation and stasis occasionally noted radiologically and at laparotomy in patients suffering from an acute attack.6 Indeed, many of the accompanying features of an acute attack are suggestive of autonomic neuropathy; namely, the inappropriate sinus tachycardia, labile hypertension, postural hypotension, excessive sweating, severe vomiting, constipation and occasional diarrhoea and sphincteric bladder problems.5 78 Ridley et al have reported that tachycardia invariably preceded the development of peripheral neuropathy and respiratory paralysis, and they postulated that the tachycardia of porphyria might be due to autonomic cardioneuropathy.5 The transient and labile hypertension which commonly accompanies the acute attack has also been given a neurogenic explanation follow-

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The acute porphyrias consists of a group of pharmacogenetic disorders of haem biosynthesis which are characterised by attacks of abdominal pain and neurological dysfunction. Although the genetic and biochemical basis of these diseases is now well established, the pathogenesis of the clinical manifestations remains speculative. Symptomatic and supportive therapy remain an important part of the management of the acute attacks. High carbohydrate intake and parenteral haematin administration are the only proven therapies that can modify an attack, both clinically and biochemically. However, haematin therapy does not provide satisfactory prophylaxis. The future use of luteinising hormone-releasing hormone (LHRH) agonists to prevent recurrent attacks in selected female patients is still under investigation.

By using a radioimmunoassay, C1-inhibitor was found to accumulate in the supernatants of human monocyte cultures. The production of this protein was inhibited reversibly by cycloheximide. When C1-inhibitor synthesis was compared with C2 synthesis, it was found that C1-inhibitor synthesis continued, whereas synthesis of C2 appeared to cease after about 7 days in culture. Immunoprecipitation of supernatants of monocyte cultures that had been pulsed with [35S]methionine showed a specific band with an Mr of 105 000. Immunoprecipitates of the lysates revealed a band of Mr 83 000; this was thought to represent a partially or non-glycosylated precursor of C1-inhibitor. C1-inhibitor produced by the monocytes was shown, by using a haemolytic assay, to be functionally active. However, the functional activity of C1-inhibitor was reduced by only 44% in the presence of cycloheximide, whereas the concentration of this protein in cycloheximide-treated culture supernatants fell by more than 93%. This finding suggests that monocytes secrete a second molecule, which inhibits C1 activity but is distinct from classical C1-inhibitor.