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Markers for vulnerability in acute porphyria. A hypothesis paper
S Thunell1, C Andersson, B Carlmark
1Porphyrias Service Sweden, Stockholm, Sweden.
European Journal of Clinical Chemistry and Clinical Biochemistry : Journal of the Forum of European Clinical Chemistry Societies
|April 1, 1995
Summary
Manganese levels are significantly higher in acute intermittent porphyria (AIP) gene carriers, regardless of symptoms. Increased cellular manganese may activate protective enzymes, but this mechanism fails in severe AIP cases, suggesting a role for oxidative stress in AIP pathogenesis.
Area of Science:
- Biochemistry
- Genetics
- Toxicology
Background:
- Acute intermittent porphyria (AIP) is linked to oxidative stress, potentially affecting hepatic and renal tissues.
- Periodic free radical overload may trigger acute neurological symptoms in AIP.
Purpose of the Study:
- To investigate variables associated with AIP symptoms in gene carriers versus controls.
- To explore the role of oxidative stress and specific mineral levels in AIP pathogenesis.
Main Methods:
- Screening of AIP gene carriers (symptomatic and asymptomatic) and matched controls.
- Analysis of leukocyte and erythrocyte concentrations of manganese, calcium, iron, and zinc.
- Statistical analysis of 78 variables to identify discriminative factors.
Main Results:
- AIP gene carriers showed significantly higher leukocyte manganese, calcium, iron, zinc, and erythrocyte calcium levels than controls.
- Cellular manganese was the most discriminative variable, explaining 98% of group variance.
- A four-fold increase in cellular manganese suggests elevated manganese-associated enzymes, potentially mitochondrial superoxide dismutase, in response to aminolaevulinic acid-derived radicals.
Conclusions:
- Elevated manganese in AIP may indicate increased mitochondrial superoxide dismutase activity, a potential defense against oxidative stress.
- This protective mechanism appears insufficient in AIP patients prone to neuropsychiatric symptoms.
- Cobalamin-folate system interactions may influence the acute porphyric process in AIP patients with a history of illness.