The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.

Abstract. Andersson C, Wikberg A, Stegmayr B, Lithner F (University Hospital, Umea Ê, Sweden). Renal symptomatology in patients with acute intermittent porphyria. A population-based study. J Intern Med 2000; 248: 319±325.Objective. Can renal insufficiency in subjects with acute intermittent porphyria (AIP) be due solely to AIP? Design. A population-based study. Subjects. Subjects with AIP $ 18 years of age (n = 386) in the four most northerly counties of Sweden.Interventions. Screening with creatinine clearance at 24 h. Patients below the lower reference level underwent a repeat clearance test and, if still low, also chromEDTA clearance. Results. 286 (74%) subjects performed the creatinine clearance test and in 57 clearance was low; the second clearance proved normal in 23 who were then excluded. Eighteen subjects with other possible medical reasons for renal insufficiency, ethical reasons or refusing further examinations were also excluded. The 16 remaining subjects with no explanation for their renal insufficiency other than AIP were then studied in detail. All 14 women, mean age 52 years, and two uraemic men, 58 and 67 years, had manifest AIP. Twelve patients had hypertension (HT) and four were normotensive in spite of renal insufficiency. Histological findings of renal biopsies revealed diffuse glomerulosclerotic and interstitial changes with additional ischaemic lesions. Conclusion. Protracted vasospasm in attacks of AIP may be a cause of renal lesions. This is discussed.

Abstract. Wikberg A, Andersson C, Lithner F (University of Umea Ê, Umea Ê; Primary Health Care Centre, Arjeplog; and University Hospital, Umea Ê, Sweden). Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria. J Intern Med 2000; 248: 27±32.Objective. To assess signs of distal neuropathy in patients with acute intermittent porphyria (AIP). Design. A population-based study. Subjects. All patients with DNA-verified AIP $ 18 years of age in the four most northerly counties of Sweden. Intervention. Validated neuropathic signs and tests such as monofilament test, neuropathic pain, dry feet, extensor digitorum brevis (EDB) test, loss of forefoot arch, hammer toes and ulceration. Results. A total of 356 patients were registered and 339 of them (95%) participated in the neuropathy study. The chronic neurological signs were symmetrical and similar to those in type 1 diabetic patients. Significant impairment was found concerning perception, EDB test, lower leg pain, ankle and knee tendon reflexes, but not concerning dry feet, loss of forefoot arch and hammer toes, on comparing patients with manifest versus latent AIP. The neurological signs were more severe in the diabetic patients (n = 298). Five AIP patients had permanent quadriplegia after severe attacks. Conclusions. Patients with manifest AIP had significantly more signs of distal chronic, symmetrical neuropathy of axonal type than did patients with latent AIP. More grave neurological lesions appear to develop after severe attacks.

The aim of this study was to elucidate the experiences of the women with severe, recurrent attacks of porphyria and how they coped with them successfully. A total of five women were interviewed and were encouraged to describe their experiences. Thematic content analysis was used to interpret the significance of their narratives. The result demonstrated that the women's experience was of living in deepest darkness with inexpressible pain, both physical and mental. Coming into contact with health care had its good and bad points. It was often difficult to cope with life during severe periods of the disease. The process of maturation towards a more positive existence seemed to follow a pattern of accepting the disease, continuing the fight until it was finally possible to discover a pattern and meaning in life that suited the individual concerned.

AIP symptoms in children may be vague and of short duration and U-ALA and U-PBG levels are often elevated only slightly or not at all; thus, symptoms and signs may differ from those in adults. Children of AIP gene carriers should be DNA tested, followed up and carefully instructed on preventive measures to avoid developing manifest AIP.