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Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Icahn School of Medicine at Mount Sinai
Rare Diseases Clinical Research Network
Office of Rare Diseases (ORD)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Icahn School of Medicine at Mount Sinai Identifier:
First received: September 14, 2012
Last updated: August 3, 2016
Last verified: August 2016
The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of the erythropoietic protoporphyrias on children and adults, and (3) to investigate the correlation between the identified genotypes and the resulting clinical presentation, also determining the possible interaction of other genetic markers.

Erythropoietic Protoporphyria
X-Linked Protoporphyria
X-Linked Dominant Erythropoietic Protoporphyria

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact

Resource links provided by NLM:

Further study details as provided by Icahn School of Medicine at Mount Sinai:

Primary Outcome Measures:
  • Clinical Analysis [ Time Frame: baseline, then annually, up to 3 years ]
    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.

Secondary Outcome Measures:
  • Laboratory Analysis [ Time Frame: baseline, then annually, up to 3 years ]
    To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype

  • Relationship between disease severity and biomarkers [ Time Frame: baseline, then annually, up to 3 years ]
    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.

Biospecimen Retention:   Samples With DNA
DNA extracted from peripheral blood sample or buccal (inside cheek) sampling for DNA analysis; whole blood in ACD anti-coagulant to establish a lymphoid cell line, red blood cells and plasma for biochemical assays.

Estimated Enrollment: 150
Study Start Date: July 2012
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Erythropoietic Protoporphyria (EPP)
Individuals with a documented diagnosis of EPP
X-Linked Protoporphyria (XLP)
Individuals with a documented diagnosis of XLP
Erythropoietic protoporphyria, unspecified
Individuals with clinical and/or biochemical diagnosis of an erythropoietic protoporphyria, but the specific type (EPP or XLP) has not been determined

Detailed Description:

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 (as in the acute or hepatic porphyrias), or cutaneous photosensitivity (as in the cutaneous porphyrias, including the erythropoietic protoporphyrias). Multiple mutations have been identified in each of the porphyrias [Anderson, 2001]. 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 [Sood 2008]. Therefore, the purpose of this study of a large group of patients with EPP and XLP 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. Much of the data collected on subjects as participants in the Longitudinal Study of the Porphyrias will be accessed for this study specific to the investigation of the erythropoietic protoporphyrias. To maximize the information that can be informative in our objectives, additional data will be collected, including additional biochemical findings and EPP-specific psychosocial parameters.

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 this study. Additional centers may be added if funding is available.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects will be recruited from the following resources:

  1. Patients followed by one of the Investigators
  2. The American Porphyria Foundation (APF)
  3. The Rare Diseases Clinical Research Network (RDCRN) Contact Registry
  4. Non-study Physician referrals
  5. Self-referrals, including family members of individuals diagnosed with Porphyria (proband) and other individuals who may have heard about the study from other subjects or prospective subjects.
  6. Medical Records Review

Inclusion Criteria:

  • All subjects must also be enrolled in the Longitudinal Study of the Porphyrias.
  • Willing to sign informed consent form
  • Biochemical findings - A marked increase in erythrocyte protoporphyrin [total erythrocyte protoporphyrin >200 ug/dL, or more than 1.5-fold increase (relative to ULN of 80 ug/dL)], with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLP).
  • Molecular findings - one of the following:

    1. A disease causing FECH mutation trans to the IVS3-48C>T low expression FECH allele
    2. Two disease-causing FECH mutations
    3. A gain-of-function ALAS-2 C-terminal deletion/exon 11 mutation (in XLP). If no mutation is found and subjects fulfill criteria 1-3 they are eligible for enrollment.

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 [Gibson 2000].
  • patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01688895

Contact: Hetanshi Naik, MS, CGC 212-659-7699
Contact: Manisha Balwani, MD 212-241-8384

United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35294-0005
Contact: Joseph R Bloomer, MD    205-996-9543   
Contact: Toni Seay, BS    205-934-7332   
Principal Investigator: Joseph R Bloomer, MD         
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: D. Montgomery Bissell, MD    415-476-8405   
Contact: Yuvraaj Kapoor    415-476-8405   
Principal Investigator: D. Montgomery Bissell, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Manisha Balwani, MD         
United States, North Carolina
Carolinas Medical Center and HealthCare System Withdrawn
Charlotte, North Carolina, United States, 28203
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27106
Contact: Herbert L Bonkovsky, MD    336-713-7341   
Contact: Denise Faust    336-713-1442   
Principal Investigator: Herbert Bonkovsky, MD         
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
Contact: Karl E Anderson, MD    409-772-4661   
Contact: Csilla Hallberg, MD    409-772-6287   
Principal Investigator: Karl E Anderson, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: John Phillips, PhD    801-585-3229   
Contact: Sharada Dixit    801-587-7252   
Principal Investigator: John Phillips, PhD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Rare Diseases Clinical Research Network
Office of Rare Diseases (ORD)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Manisha Balwani, MD Icahn School of Medicine at Mount Sinai
  More Information

Additional Information:
Responsible Party: Icahn School of Medicine at Mount Sinai Identifier: NCT01688895     History of Changes
Other Study ID Numbers: GCO 08-0959-04
HSM12-00307 ( Other Identifier: Mount Sinai School of Medicine )
U54DK083909 ( US NIH Grant/Contract Award Number )
Study First Received: September 14, 2012
Last Updated: August 3, 2016

Keywords provided by Icahn School of Medicine at Mount Sinai:

Additional relevant MeSH terms:
Protoporphyria, Erythropoietic
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Metabolic Diseases processed this record on April 24, 2017