Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP)

Study Overview
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Brief Summary
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Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease, which is relatively prevalent in northern Norway with a total of around 90 patients. This provides us with a special opportunity to study AIP. AIP is caused by a mutation in the porphobilinogen deaminase, an enzyme in the haem synthesis. AIP presents symptoms, particularly among fertile women and older men. Typical symptoms are abdominal pain and dark red urine, nausea, vomiting, constipation, muscle weakness and nerve damage including paraesthesia and even paresis. This is known as symptomatic or manifest AIP (MAIP). Others do not display symptoms, so-called latent AIP (LAIP). AIP attacks may be triggered by a host of medicaments which affect the haem synthesis, infections, alcohol and stress. Treatments of manifestations include high sugar intake (4 sugar lumps/hour), alternatively administer glucose and Normosang (synthetic haem arginate) by intravenous injection and removing triggering factors. Diet, glucose intake, dental health and inflammatory parameters will be examined. This study can provide new knowledge about why only some people develop symptoms of AIP. Main hypothesis: There are differences in the diet, iron status, inflammation and glucose metabolism of the MAIP group vs. the LAIP group and the control group.

Detailed Description
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In a group of people with proven acute intermittent porphyria (AIP) mutation, some will remain asymptomatic, while others have repeated periods of porphyria symptoms. Glucose inhibits ALA synthetase (ALAS), the first rate-limiting enzyme in the haem synthesis. Studies of individual patients point to the fact that increased glucose and/or fructose content in the diet inhibits porphyria attacks. A high sugar intake can reduce the disease activity in patients with AIP. The diet and related biomarkers of those with latent and manifest AIP will therefore be mapped to explain why some have latent and others have manifest acute intermittent porphyria. Other studies point to the fact that people with manifest AIP who have later developed diabetes type 2 no longer have porphyria symptoms. Dental health will also be examined. Inflammation also affects the haem synthesis. Infections and/or inflammation are known to trigger AIP attacks. The disease activity in patients with acute intermittent porphyria in relation to inflammatory status, iron status, glucose metabolism and diet will therefore be examined. The iron metabolism is interesting to study because it is believed that the overstimulation of the haem synthesis is what triggers porphyria attacks. Haem consists of iron and protoporphyrin IX, and it is therefore possible that iron supplements in cases of iron deficiency can induce increased haem synthesis and by doing so trigger and/or aggravate AIP. Kidney failure is a serious secondary complication in some patients with MAIP. Protein markers for kidney injury in urine will be examined.

Official Title
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Dental Health, Diet, Inflammation and Biomarkers in Patients With Acute Intermittent Porphyria(AIP)

Conditions
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Acute Intermittent Porphyria

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed acute intermittent porphyria Exclusion Criteria: Regulatory use of antiinflammatory drugs including steroids and NSAIDS Lacking consent competence

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control group<br>Healthy control group, matched for age and gender | |
| Acute intermittent porphyria<br>Patients with acute intermittent porphyria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Resting systolic and diastolic blood pressure, a number of inflammatory parameters, serum markers for iron status and inflammation | Within 2 months after inclusion | 
| Diet registration | Dietary registration during one week | Within 2 months after inclusion | 
| Iron status | Blood samples for evaluation of iron status | Within 2 months after inclusion | 
| Inflammatory status | Blood samples (cytokines etc) for evaluation of inflammation | Within 2 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dental health | Evaluate dental health through clinical examination | Within two months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Porphyria, Inflammation, Diet, Iron status