The Porphyrias Consortium

7204: Clinical Diagnosis of Acute Porphyria

Status: Recruiting

Background

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 (also referred to as the "index case", 50% of whom are expected to carry the same genetic defect of the index case.
  • To devise a Genetic Carrier 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

About this Study

This is a longitudinal study of approximately 600 people that will consist of two parts.

Part 1:
We will enroll individuals who are first-degree relatives (child, sibling, parent, or grandparent) of a patient with a diagnosis of one of the acute porphyrias (index case). We are interested in all three types of acute porphyria in which the index case has been confirmed by genetic testing: Acute Intermittent Porphyria (AIP), Hereditary Corproporphyria (HCP) or Variegate Porphyria (VP). Participants (the first-degree relatives) must not have had any genetic testing as yet. They will have an initial visit during which they will complete a history questionnaire and have routine laboratory tests, including genetic testing for porphyria. The researchers will use this data to develop a Clinical Profile of the risk factors associated with being a genetic carrier of acute porphyria.

Part 2:
Researchers will test the validity of the Clinical Profile. This part of the study will include subjects who are thought to possibly have AIP or HCP, but do not have a confirmed diagnosis based on genetic testing.

Follow Up Sub-Study:
In addition to Parts 1 and 2 of this study, we will conduct a separate follow up assessment of patients who have been seen by one of the Porphyria Consortium physicians / investigators 10 or more years ago, but were not given a diagnosis of porphyria at the time of that visit. The purpose of this assessment is to determine if some of these patients subsequently did receive a confirmed diagnosis of acute porphyria. We are interested also in other diagnoses that may have emerged over the 10+ years, which now explain the minor elevations of porphyrin tests and recurrent abdominal pain.

Participation in Parts 1 and 2 of the study will include the following:

  • A physical exam
  • Answering questions about your health and quality of life
  • Donation of samples for laboratory evaluations, including samples of blood, urine, and stool
  • Donation of a blood sample for genetic testing (first visit only)
  • Review of your medical records

All participants will be evaluated once a year for up to five years. Subjects who are found not to have porphyria will have only the first visit. There is no interventional treatment involved with this study.

Participation in the Follow Up Sub-Study will include the following:

  • Review of your medical records
  • A one time completion of an acute porphyria questionnaire

Targeted Enrollment

To be eligible to participate in Part 1, you must:

  • Be 15 years of age or older
  • Be a first-degree relative (child, sibling, parent, or grandparent) of an individual with genetically proven acute porphyria (AIP, HCP or VP)
  • Not have had any previous genetic testing for acute porphyria

To be eligible to participate in Part 2, you must:

  • Be 15 years of age or older
  • Have a history of suggestive clinical features, such as abdominal, back or limb pain, recurrent nausea lasting days, reaction to medications, psychiatric history, or sun sensitivity.
  • An increase in urinary, fecal or serum porphobilinogen (PBG) and/or porphyrins

To be eligible to participate in the Follow Up Sub-Study, you must:

  • Have been seen by one of the Porphyria Consortium physicians/investigators 10 or more years prior to study initiation
  • Had a slight increase in porphyrins during the initial visit
  • Not given a diagnosis of porphyria at the time of the visit

You are not eligible to participate in the Follow Up Sub-Study if:

  • You have been seen by the Porphyria Consortium physician/investigator less than 10 years prior to study initiation.

How to participate:

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.

California

 

The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.