Acute intermittent porphyria. Inflammation, diet and biomarkers in acute intermittent porphyria

Abstract

Acute intermittent porphyria (AIP) is a rare autosomal dominant inherited metabolic disease with lowered function of the enzyme hydroxymethylbilan synthase due to mutation in this gene of the heme synthesis. The resulting excess of aminolevulinic acid and porphobilinogen can result in acute abdominal pain, paresis, fatigue, increased risk for kidney failure and hepatocellular carcinoma. Some drugs, fasting, infections and stress can trigger AIP attacks. Metabolic diseases like diabetes mellitus are associated with inflammation. Therefore we investigated if there was inflammation in AIP measured as elevated levels of plasma cytokines. Handling of blood samples can have effect on the cytokine levels, so we compared the use of plasma using four different anticoagulants with serum. The effects of storage temperature, freezing and thawing were also examined. We concluded that one should analyse cytokines in EDTA plasma samples stored at 4ºC for up to 4 hours before centrifugation. We established reference ranges for cytokines from 162 healthy persons. By using a multiplex assay, we found elevated cytokines in the 50 AIP cases as a sign of low-grade inflammation, compared to the 50 matched controls. The inflammation may be one of the explanations for the higher risk for HCC in AIP. We found lower levels of prealbumin and lower kidney function in symptomatic vs. asymptomatic AIP cases. The fasting C-peptide and insulin levels were lower in the symptomatic AIP cases compared to matched controls. Persons with AIP are recommended a high carbohydrate intake because glucose inhibits the first step in the heme synthesis. The cases and controls filled out a 7-days diet logbook, had their anthropometric measures done, filled out a questionnaire on lifestyle-factors and was interviewed by a physician. Blood was analysed for cytokines, vitamins, glucose metabolism measures and fats etc. Persons with AIP had a lower carbohydrate intake than recommended by guidelines.