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.

The objectives of this study were to investigate the lifetime prevalence of epileptic seizures in a population with acute intermittent porphyria (AIP) and to characterize the seizures and the seizure-triggering factors. A letter was sent to all patients with known AIP in Sweden registered at the National Porphyria Center (n = 294). The medical records of patients who had had epileptic seizures were reviewed in detail. The letter was answered by 268 patients (91.2%). Ten patients (3.7%) reported epileptic seizures. Eight were women (mean age 54.1 years, range 30-81 years), and 2 were men (mean age 19 years, range 9-29 years). Six patients had tonic-clonic seizures and 4 had partial seizures becoming secondarily generalized. Serum sodium levels were low in 3 patients (mean 110, range 103-120 mM), and normal in 5. Excretion of 5-aminolevulinic acid (ALA) in the urine was increased in 4 patients at the time of the seizures. In 6 patients, the seizures were associated with an acute attack of AIP (all patients with hyponatremia included). The lifetime prevalence of AIP-associated seizures was 2.2% of all those with known AIP and 5.1% of all those with manifest AIP. Epileptic seizures among persons with AIP are less common than has been previously described.

This study raises the possibility that diabetes mellitus may be beneficial for patients with severe AIP.

Background: Case reports display similaritiesbetween multiple sclerosis and acute intermittent porphyria (AIP). This study examines whether patients with AIP in general demonstrate white-matter lesions on brain magnetic resonance imaging (MRI) and/or abnormalities in plasma and/or cerebrospinal fluid (CSF) when examined outside attacks. We looked particularly for the presence of oligoclonal bands (OB) of immunoglobulin (Ig) in liquor. Methods:Eight AIP gene carriers without previous episodes of porphyria, mean age 42.8 years (range 30–60), and 8 AIP gene carriers with previous episodes of porphyria, mean age 42.8 years (range 33–62), were examined with brain MRI, venous blood samples and lumbar punctures. Results: Two male AIP gene carriers with previous episodes of porphyria, 58 and 35 years of age, had multiple white-matter, high-signal lesions on T₂- weighted MRI sequences. Two AIP gene carriers without previous episodes of porphyria, 1 male and 1 female, had less than 5 such lesions. No OB were seen in the CSF in any patient, but 1 carrier had an increased level of protein in the CSF. Seven of 16 subjects (44%) had increased levels of HbA1c (>6.0), suggesting protracted hyperglycemia, and 3 further subjects had borderline levels (5.9). Conclusion: T₂-weighted MRI sequences demonstrated multiple white-matter, high-signal lesions in 4 out of 16 AIP gene carriers (25%). No carrier demonstrated OB of Ig in CSF, making it unlikely that demyelinating lesions play a pivotal role in the pathogenesis of CNS symptoms in AIP. Only 1 AIP gene carrier had an increased level of protein in CSF; this contrasts with studies during acute attacks of porphyria. Seven subjects (44%) had abnormally high levels of HbA1c, in spite of the fact that no patient had a previous diagnosis of diabetes mellitus.

Background: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke. Methods: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011. Results: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99–2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03–2.21). Conclusion: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.