Clinical Trial: Clinical Diagnosis of Acute Porphyria

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Clinical Diagnosis of Acute Porphyria

Brief Summary: 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.

Detailed Summary:

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

Sponsor: University of California, San Francisco

Current Primary Outcome:

• 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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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&nbs
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome:

  • Frequency of disease manifestations in genetically confirmed AIP and HCP [ Time Frame: Assessed annually for 5 years ]
    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. ]
    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.
  
  
  

  Original Secondary Outcome: Same as current
  
  Information By: University of California, San Francisco
  

  Dates:
  Date Received: February 16, 2012
  Date Started: December 2011
  Date Completion: December 2018
  Last Updated: September 23, 2013
  Last Verified: September 2013