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 ]
  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 Frame: Assessed once during a one-time telephone or in-person interview ]
  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 ]
  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. ]
  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 ]
  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.
  
  

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