Longitudinal Study of the Porphyrias

• clinical analysis [ Time Frame: baseline ] [ Designated as safety issue: No ]
  To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.
  
  
• clinical analysis [ Time Frame: year 1 ] [ Designated as safety issue: No ]
  To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.
  
  
• clinical analysis [ Time Frame: year 2 ] [ Designated as safety issue: No ]
  To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.
  
  
• clinical analysis [ Time Frame: year 3 ] [ Designated as safety issue: No ]
  To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.
  
  
• clinical analysis [ Time Frame: year 4 ] [ Designated as safety issue: No ]
  To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.
  
  
• Laboratory analysis [ Time Frame: baseline ] [ Designated as safety issue: No ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  
  
• Laboratory analysis [ Time Frame: year 1 ] [ Designated as safety issue: No ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  
  
• Laboratory analysis [ Time Frame: year 2 ] [ Designated as safety issue: No ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  
  
• Laboratory analysis [ Time Frame: year 3 ] [ Designated as safety issue: No ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  
  
• Laboratory analysis [ Time Frame: year 4 ] [ Designated as safety issue: No ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  
  

• Relationship between disease severity and biomarkers [ Time Frame: baseline ] [ Designated as safety issue: No ]
  To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.
  
  
• Relationship between disease severity and biomarkers [ Time Frame: year 1 ] [ Designated as safety issue: No ]
  To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.
  
  
• Relationship between disease severity and biomarkers [ Time Frame: year 2 ] [ Designated as safety issue: No ]
  To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.
  
  
• Relationship between disease severity and biomarkers [ Time Frame: year 3 ] [ Designated as safety issue: No ]
  To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.
  
  
• Relationship between disease severity and biomarkers [ Time Frame: year 4 ] [ Designated as safety issue: No ]
  To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.
  
  
• Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: baseline ] [ Designated as safety issue: No ]
  Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
• Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 1 ] [ Designated as safety issue: No ]
  Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
• Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 2 ] [ Designated as safety issue: No ]
  Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
• Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 3 ] [ Designated as safety issue: No ]
  Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
• Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 4 ] [ Designated as safety issue: No ]
  Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  

The porphyrias are a group of rare metabolic diseases that may present in childhood or adult life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common manifestations are related to accumulation of intermediates in the pathway and usually occur as acute neurological attacks, or cutaneous photosensitivity. Multiple mutations have been identified in each of the porphyrias. The risk of disability or death from these disorders is significant, in part because diagnosis is often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover, the natural history of these disorders is not well described and it is not known what determines differences in outcomes. New therapies are needed. For existing therapies, high-quality evidence on short and long term efficacy and safety is generally lacking. Therefore, the purpose of this long-term follow-up study of a large group of patients with the various porphyrias is to provide a better understanding of the natural history of these disorders, as affected by available therapies, and to aid in developing new forms of treatment.

The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes and currently has funded 19 rare diseases clinical research consortia and one Data Management and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions listed in the participating institutions table. All Centers in the Porphyrias Consortium are participating in the Longitudinal Study of the Porphyrias. Additional centers may be added if funding is available.

The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of specific porphyrias for clinical, biochemical, and genetic studies. The long-term objective is to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with acute and cutaneous porphyria.