Key Terms and Definitions in Acute Porphyrias: Results of an International Delphi Consensus Led by the European Porphyria Network

Background: Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and in clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. Methods: The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by 2 Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. Results: 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of 9 terms and definitions. 34 experts were invited to take part in the Delphi rounds. 7 of the initial 9 terms and definitions which entered the first Delphi round achieved the threshold for agreement. Following a second Delphi round, all 9 definitions achieved agreement. Conclusion: Agreement on the definitions for 9 important terms describing acute porphyrias represents a significant step forward for the porphyria community. It will facilitate more accurate comparison of outcomes among porphyria centres and in clinical trials and provide a strong framework for developing evidence based clinical guidelines.Background: Acute porphyrias are a group of rare inherited disorders causing acute neurovisceral attacks. Many terms used frequently in the literature and in clinical practice are ambiguous, which can lead to confusion in the way patients are managed, studied, and reported in clinical studies. Agreed definitions are a necessary first step in developing management guidelines and will facilitate communication of results of future clinical research. Methods: The Delphi method was used to generate consensus on key terms and definitions in acute porphyria. The process started with a brainstorming phase offered to all members of the European Porphyria Network followed by 2 Delphi rounds among international experts in the field of porphyria (the Acute Porphyria Expert Panel). A consensus of 75% or more was defined as the agreement threshold. Results: 63 respondents from 26 countries participated in the brainstorming phase, leading to the choice of 9 terms and definitions. 34 experts were invited to take part in the Delphi rounds. 7 of the initial 9 terms and definitions which entered the first Delphi round achieved the threshold for agreement. Following a second Delphi round, all 9 definitions achieved agreement. Conclusion: Agreement on the definitions for 9 important terms describing acute porphyrias represents a significant step forward for the porphyria community. It will facilitate more accurate comparison of outcomes among porphyria centres and in clinical trials and provide a strong framework for developing evidence based clinical guidelines

DENATURING GRADIENT GEL-ELECTROPHORESIS FOR RAPID DETECTION OF LATENT CARRIERS OF A SUBTYPE OF ACUTE INTERMITTENT PORPHYRIA WITH NORMAL ERYTHROCYTE PORPHOBILINOGEN DEAMINASE ACTIVITY

Acute intermittent porphyria is an autosomal dominant disorder defined by a partial deficiency of porphobilinogen deaminase (EC 4.3.1.8). Clinical manifestations of the disease are characterized by acute attacks of neurological dysfunction often linked to environmental factors. Early diagnosis of gene carriers is important in the prevention of attacks and is usually achieved by determining the porphobilinogen deaminase activity in erythrocytes. However, in a subtype of acute intermittent porphyria, the enzymatic defect is restricted to nonerythropoietic cells. Different mutations have already been described that account for this phenotype in two unrelated families. We previously detected asymptomatic carriers by using mutation-specific probes after in vitro amplification of the target DNA sequence. In this study, we investigated the DNA of eight unrelated subjects with the same subtype of acute intermittent porphyria by using the polymerase chain reaction, with subsequent analysis of the amplified products by denaturing gradient gel electrophoresis. Five of these patients shared the same single-base change. This technique was quite simple and efficient for detecting asymptomatic carriers. Importantly, it is potentially useful for studying families with the same phenotypic subtype of the disease and possibly different mutations in the same DNA region

Ancestral founder of mutation W283X in the porphobilinoge deaminase gene among acute intermittent porphyria patient.

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