Diagnosis of variegate porphyria - hard to get?

Variegate porphyria (VP) is an inherited metabolic disease that results fro m the partial deficiency of protoporphyrinogen oxidase. In this communicati on we have used DNA technology in the diagnosis of VP and compared the resu lts with the biochemical and clinical data. To date, we have diagnosed 107 VP patients using either biochemical or DNA techniques or both. In addition , in 106 family members the diagnosis of VP could be excluded. The sensitiv ity and specificity of the biochemical screening for VP were studied among 38 family members. These individuals were either asymptomatic (n=19) or had experienced occasional skin symptoms (n=13), acute attacks (n=5) or both ( n=1). The sensitivity of urinary and fecal coproporphyrin analysis was 48% and 52%, respectively. The sensitivity of urinary uroporphyrin analysis was 71% and for fecal protoporphyrin 77%. Plasma fluorescence was sensitive in symptomatic patients even in remission, but resulted in false negatives in four asymptomatic patients with normal excretion of porphyrins in the urin e. In our series of mutation screening, many new asymptomatic patients were identified, and this demonstrated that DNA analysis is the only reliable w ay to screen (a)symptomatic patients facilitating correct treatment and pro per genetic counselling of family members at risk. Biochemical analyses (e. g. plasma fluorescence, fecal protoporphyrins, urinary copro- and uroporphy rins, porphobilinogen and delta-aminolevulinic acid) are essential when the diagnosis of VP is confirmed at the symptomatic phase.