Summary
The acute porphyrias are four rare disorders which are characterized by an inborn enzymatic error of the biosynthesis of heme. In Europe, acute intermittent porphyria represents the main subtype of the acute porphyrias, whereas variegate porphyria and hereditary coproporphyria are less common. Concerning 5-aminolevulinic-acid-dehydratase-deficient porphyria less than ten cases have been described worldwide. Normally, acute porphyrias remain clinically inapparent during the whole lifetime. Under certain environmental circumstances (e. g., pharmacological, endocrine or nutritional factors), they might produce attacks with varying gastrointestinal, neurological and/or psychiatric symptoms. Such an attack can progress into a life-threatening crisis with quadraparesis, respiratory arrest, SIADH, hyponatriemia, seizures and/or cardiac arrhythmia. Each attack of an acute porphyria can be definitely diagnosed by urine analysis of porphobilinogen and 5-aminolaevulinic acid, which however needs initial clinical suspicion. Early treatment contributes to—but not necessarily guarantees—a rapid remission of the attack. The treatment comprises avoidance of any precipitating factor and administration of heme arginate or high-dose glucose infusions which interrupt the dysregulated hepatic heme biosynthesis.
Zusammenfassung
Die akuten Porphyrien umfassen eine Gruppe von vier seltenen Stoffwechselerkrankungen mit einem angeborenen Defekt innerhalb der achtstufigen Hämbiosynthese. In Europa ist der häufigste Subtyp die Akute Intermittierende Porphyrie. Die Porphyria Variegata und die Hereditäre Koproporphyrie sind weitaus seltener. Zur 5-Aminolävulinsäure-Dehyratase-Defizienz-Porphyrie existieren weltweit weniger als zehn Fallberichte. In der Regel bleiben die akuten Porphyrien zeitlebens klinisch inapparent. Nur unter bestimmten Umständen (z. B. Medikamente, endokrine Faktoren, Mangelernährung oder Nikotinabusus) treten sie in Form sogenannter Attacken mit dann schwersten Bauchschmerzen und/oder neurologischen bzw. psychiatrischen Symptomen in Erscheinung. Das klinische Bild der porphyrischen Attacke ist variabel; gefürchtete Komplikationen sind Tetraparese unter Einbeziehung der Atemmuskulatur, SIADH mit Hyponatriämie und Krampfanfälle oder kardiale Arrhythmien. Eine porphyrische Attacke lässt sich anhand einer Urinanalyse auf Porphobilinogen und 5-Aminolävulinsäure diagnostisch bestätigen oder ausschließen; dies setzt jedoch einen aktiven klinischen Anfangsverdacht voraus. Die umgehende Einleitung einer kausalen Therapie trägt zur frühzeitigen Remission einer Attacke bei, sie ist jedoch keine Garantie dafür. Therapiemaßnahmen umfassen neben dem sofortigen Absetzen jeglicher potenziell porphyrinogener Faktoren die Gabe von Hämarginat mit ggf. zusätzlich hochdosierter Glukose, wodurch die fehlregulierte hepatische Hämbiosynthese durchbrochen wird.
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Serie: Die Notfall- und Intensivtherapie bei endokrinen und metabolischen Erkrankungen Herausgegeben von J. Schölmerich und U. Woenckhaus (Regensburg)
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Bollheimer, L.C., Reng, C.M. Die akuten hepatischen Porphyrien in der Notfall- und Intensivmedizin. Intensivmed 41, 388–405 (2004). https://doi.org/10.1007/s00390-004-0478-4
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DOI: https://doi.org/10.1007/s00390-004-0478-4
Key words
- Heme biosynthesis
- acute intermittent porphyria
- variegate porphyria
- hereditary coproporhyria
- porphyrinogenic drugs
- heme arginate