7207 - EPP: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact


Status: Recruiting
Keywords: Erythropoietic Protoporphyrias
IRB Number: 00059196
Specialty: Hematology/BMT
Sub Specialties:

Brief Summary

This is an ancillary study of the Longitudinal Study of the Porphyrias (IRB#45117).

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.

Principal Investigator: Charles Parker
Department: Hematology
Co Investigator: John Phillips

Contact Information

Name:Jeanette Davis
Phone: 801-587-7525
Email: jeanette.davis@hsc.utah.edu

Inclusion Criteria

1.  Clinical Features - a or b required
a. A history of nonblistering cutaneous photosensitivity.
b. A diagnosis of EPP or XLP in a relative

2.  Biochemical findings - a or b required
a.  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/dL0], with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLP).
b.  Increased plasma porphyrins in almost all cases and a fluorescence emission peak at ~635 nm.
c.  Normal urinary porphyrins (except in patients with hapatobiliary impairment), and normal ALA and PBG.

3.  Molecular findings - one of the following:
a.  A disease causing FECH mutation trans to the IVS3-48C>T low expression FECH allele
b.  Two disease-causing FECH mutations
c.  A gain-of-function ALAS-2 C-terminal deletion/exon 11 mutation (XLP).

Others who may be enrolled:
1.  Relatives who may be asymptomatic but may share genetic traits, including disease-causing mutation, as demonstrated by DNA in an index case.
2.  Possible but unconfirmed cases that meet some but not all diagnostic criteria for a definite diagnosis;  these are likely to be informative as a comparison group.

Exclusion Criteria

1.  Patients 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.

2. Patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.