Clinical Diagnosis of Acute Porphyria
The purpose of this study is to test whether a focused questionnaire and laboratory tests can better define risk factors associated with possible genetic porphyria. The investigators hypothesize that the genetic carrier state of acute porphyria is distinctive enough that the Genetic Carrier Profile the investigators devise through this study will be useful in identifying carriers of genetic porphyria among the large population with undiagnosed abdominal pain.
Hereditary Coproporphyria (HCP)
Acute Intermittent Porphyria (AIP)
Variegate Porphyria (VP)
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Clinical Diagnosis of Acute Porphyria|
- Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]All subjects will be assessed for any elevation of quantitative urine porphobilinogen (PBG).
- Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]All subjects will be assessed for any elevations of fractionated quantitative urine porphyrins.
- Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]All subjects will be assessed for any elevations and levels of fractionated quantitative fecal porphyrins.
- Clinical features suggestive of the acute porphyria carrier state [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]Through a focused questionnaire, we will determine the typical duration of pain attacks.
- Acute porphyria genetic carrier state [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]All subjects will undergo DNA analysis to detect a mutation in the HMBS, CPOX, or PPOX genes, respectively.
- Other possible causes of mildly elevated porphyrins and recurrent pain [ Time Frame: Assessed once during a one-time telephone or in-person interview ] [ Designated as safety issue: No ]Participants in the Follow-up Sub-study section of this protocol will be interviewed concerning other possible causes of mildly elevated porphyins and recurrent pain. These will be patients previously seen by the investigator who were deemed not to have porphyria.
- Presence of heavy metals [ Time Frame: Assessed once at baseline visit for all subjects ] [ Designated as safety issue: No ]All subjects will undergo a blood test to screen for the presence of heavy metals as a cause for minor elevations of porphyrin levels.
- Validity of Genetic Carrier Profile [ Time Frame: The profile will be tested once during the baseline visit for subjects in Group 2. ] [ Designated as safety issue: No ]The biochemical and clinical features of genetically proven but asymptomatic HCP will be tabulated and compared to subjects who are not genetic carriers. Its accuracy in predicting risk factors for HCP will be tested in subjects in Group 2.
- Frequency of disease manifestations in genetically confirmed AIP and HCP [ Time Frame: Assessed annually for 5 years ] [ Designated as safety issue: No ]Subjects who are confirmed to have AIP and HCP will be assessed at annual follow up visits for the presence and frequency of porphyria symptoms.
- Prevalence of HCP in a population with elevation of urine coproporphyrin and pain symptoms. [ Time Frame: Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period. ] [ Designated as safety issue: No ]Based on the number of subjects in Group 2 determined by DNA analysis to have HCP, we will approximate the prevalence of HCP in a population with elevations in coproporphyrin and pain symptoms that are undiagnosed.
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Group 1 will include subjects 15 years of age or older who are a first-degree relative (child, sibling, parent, or grandparent) of an individual with genetically proven acute porphyria (AIP, HCP or VP), and have not had any previous genetic testing for porphyria themselves.
Group 2 (Not Yet Enrolling)
Group 2 will consist of subjects 15 years of age or older who have a history of clinical features suggestive of acute porphyria, such as such as abdominal, back or limb pain, recurrent nausea lasting days, reaction to medications, psychiatric history, or sun sensitivity, and an increase in urinary, fecal or serum porphobilinogen (PBG) and/or porphyrins.
Subjects in Group 3 will participate in the "Follow Up Sub-Study." This group will include individuals who have been seen by one of the Porphyria Consortium physicians/investigators for suspicion of porphyria 10 or more years prior to study initiation, but were not given a diagnosis of porphyria at the time of their initial visit.
The porphyrias are a group of genetic diseases caused by disturbances in the formation of heme, an essential component of hemoglobin and other proteins, leading to either acute (neurologic) and/or chronic (cutaneous) symptoms. Acute porphyria is often difficult to diagnose because symptoms may not be specific and, unless the patient is in an active attack, laboratory values typically may not be useful for diagnosing porphyria. The purpose of this study is to test whether a focused questionnaire and laboratory evaluation tool can better define risk factors associated with possible genetic porphyria. The goals of this study are:
- To determine the presence and number of abnormal lab tests and porphyria-like symptoms in adult family members of the first person in a family who has been diagnosed with a disease of acute porphyria, 50% of whom are expected to carry the same genetic defect of the index case.
- To devise a Genetic Carrie Profile that could be used to screen people in whom the diagnosis of porphyria is being considered.
- To test the Profile in patients with symptoms suggestive of HCP and/or urine tests showing some elevation of porphyrins.
- To explain other possible causes of minor increases in porphyrin levels in patients with recurrent abdominal pain who have not been diagnosed with porphyria
|Contact: Dana O Doheny, M.S., C.G.C.||(212) firstname.lastname@example.org|
|Contact: Theora B Cimino||(415) 307-4526||PorphyriaCenter@ucsf.edu|
|United States, Alabama|
|UAB Porphyria Center, University of Alabama at Birmingham||Not yet recruiting|
|Birmingham, Alabama, United States, 35294|
|Contact: Toni Seay 205-996-9543 email@example.com|
|Principal Investigator: Joseph R. Bloomer, M.D.|
|United States, California|
|UCSF Porphyria Center, University of California at San Francisco||Recruiting|
|San Francisco, California, United States, 94143|
|Contact: Theora B Cimino 415-476-8405 PorphyriaCenter@ucsf.edu|
|Principal Investigator: D. Montgomery Bissell, M.D.|
|United States, New York|
|Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine||Recruiting|
|New York, New York, United States, 10029|
|Contact: Dana O Doheny, M.S., C.G.C. 212-659-6779 firstname.lastname@example.org|
|Principal Investigator: Robert J. Desnick, Ph.D., M.D.|
|United States, North Carolina|
|Carolinas Medical Center and HealthCare System||Not yet recruiting|
|Charlotte, North Carolina, United States, 28203|
|Contact: Gale Groseclose, R.N. 704-355-4875 Gale.Groseclose@carolinashealthcare.org|
|Contact: Regina McFadden (704) 355-7608 Regina.Mcfadden@carolinashealthcare.org|
|Principal Investigator: Herbert L. Bonkovsky, M.D.|
|United States, Texas|
|UTMB Porphyria Center, University of Texas Medical Branch||Not yet recruiting|
|Galveston, Texas, United States, 77555|
|Contact: Csilla Hallberg, M.D. 409-772-4661 email@example.com|
|Principal Investigator: Karl E. Anderson, M.D.|
|United States, Utah|
|Porphyria Center, University of Utah||Not yet recruiting|
|Salt Lake City, Utah, United States, 84132|
|Contact: Jeanette Buehler 801-587-7525 jeanette.Buehler@hsc.utah.edu|
|Principal Investigator: John Phillips, M.D.|
|Study Chair:||D. Montgomery Bissell, M.D.||University of California at San Francisco|
|Principal Investigator:||Karl E. Anderson, M.D.||University of Texas|
|Principal Investigator:||Joseph R. Bloomer, M.D.||University of Alabama at Birmingham|
|Principal Investigator:||Robert J. Desnick, Ph.D., M.D.||Mount Sinai School of Medicine|
|Principal Investigator:||James P. Kushner, M.D.||University of Utah|
|Principal Investigator:||Herbert L. Bonkovsky, M.D.||Carolinas Medical Center and HealthCare System|