Longitudinal Study of the Porphyrias

Icahn School of Medicine at Mount Sinai1,500 enrolled

Overview

The objective of this protocol is to conduct a longitudinal multidisciplinary investigation of the human porphyrias including the natural history, morbidity, pregnancy outcomes, and mortality in people with these disorders.

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 several 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.

Study Type

OBSERVATIONAL

Enrollment

1,500

Conditions

Acute Porphyrias Cutaneous Porphyrias

Eligibility

Sex: ALLMin age: 1 Minute

Medical Language ↔ Plain English

Inclusion Criteria: * Individuals with a documented diagnosis of a porphyria. * For each type of porphyria, the inclusion criteria are based on * Biochemical findings, as documented by laboratory reports (or copies) of porphyria-specific testing performed after 1980 (Absolute values are preferred for diagnostic biochemical thresholds. Fold increases in comparison to an upper (or lower) limit of normal (ULN or LLN) are also acceptable, but are complicated by considerable variation between laboratories in normal limits. Equivocal biochemical measurements may require confirmation by a consortium reference laboratory;) * molecular findings documenting the identification of a mutation in a porphyria-related gene. * In addition, an individual or a parent or guardian must be willing to give written informed consent or assent, as appropriate. * Provision is made for enrolling relatives who may not have symptoms but have biochemical or molecular documentation of a porphyria, or in the case of recessive disorders carry a disease-related mutation. Exclusion Criteria: * Cases with elevations of porphyrins in urine, plasma or erythrocytes due to other diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone marrow diseases; * Patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.

Locations (15)

University of Alabama, Birmingham

Birmingham, Alabama, United States

RECRUITING

University of California, Los Angeles

Outcomes

Primary Outcomes

clinical analysis

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.

Time frame: baseline

Laboratory analysis

To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype

Time frame: baseline

Secondary Outcomes

Relationship between disease severity and biomarkers

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.

Time frame: baseline

Effectiveness and tolerability of currently used and new therapies for the human porphyrias

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.

Time frame: baseline

Central Contacts

Mary Freeman, MS, CGC

CONTACT

212-659-1434 mary.freeman@mssm.edu

Data from ClinicalTrials.gov

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