Effect of Isoniazid on Protoporphyrin Levels in Erythropoietic Protoporphyria (INHEPP)

Inclusion Criteria:

• All subjects will be enrolled in the Longitudinal Study of the Porphyrias.

• In patients with EPP the inclusion criteria are based on

  1. clinical features
  2. biochemical findings, as documented by laboratory reports of porphyria-specific testing performed after 1980
  3. molecular findings documenting the identification of a mutation in FECH or ALAS2 genes (molecular evidence of EPP is required for inclusion in the study).

These data will be obtained from the Porphyria Rare Disease Clinical Research Consortium Longitudinal Study (RDCRN Protocol 7201). An individual must be willing to give written informed consent and be 18 years of age or greater.

Autosomal EPP (EPP) and X-linked protoporphyria (XLEPP)

Clinical features - a or b required

• A history of nonblistering cutaneous photosensitivity, usually with early age of onset.
• A diagnosis of EPP or XEPP in a relative.

Biochemical findings

• A marked increase in erythrocyte protoporphyrin [total erythrocyte protoporphyrin >200 ug/dL, or more than 1.5-fold increase relative to upper limit of normal of 80 ug/dL, with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLEPP). Note: Methods in some laboratories for measuring free erythrocyte protoporphyrin (FEP) actually measure zinc protoporphyrin, so these results cannot be relied upon for diagnosis or characterizing the phenotype in EPP and XLEPP.
• Increased plasma porphyrins with a fluorescence emission peak at ~634 nm.
• Normal urinary porphyrins (except in patients with hepatobiliary impairment), and normal ALA and porphobilinogen (PBG).

Molecular findings - one of the following:

• A disease causing FECH mutation trans to the IVS3-48C>T low expression FECH allele (aEPP)
• Two disease-causing FECH mutations (EPP, recessive variant)
• A gain-of-function ALAS2 C-terminal deletion/exon 11 mutation (XLEPP)

Exclusion Criteria:

• We will exclude patients with a diagnosis of EPP that cannot be documented by DNA testing.
• Patients with evidence of active liver injury as defined by serum transaminase concentrations greater than three times the upper limit of normal, those with a history of recent (within 3 months of enrollment) or ongoing alcohol abuse, those with diabetes mellitus requiring therapy, renal insufficiency (serum creatinine >2.0 mg/ml) or evidence of malnutrition (based on subnormal plasma concentration of transthyretin) will be ineligible for participation in the study.
• Pregnant and/or lactating women will be excluded from the study.