1/2. Overrepresentation of the founder PPOX gene mutation R59W in a South African patient with severe clinical manifestation of porphyria.A patient, who presented with abdominal pain and severe photosensitivity that resulted in scarring and mutilation of the fingers, nose and ears, was referred for biochemical assessment of porphyria and dna screening. Although these clinical manifestations were suggestive of both acute porphyria and congenital erythropoietic porphyria, the biochemical profile was consistent with variegate porphyria (VP). Analysis of the protoporphyrinogen oxidase (PPOX) gene underlying VP resulted in the identification of the founder mutation R59W in a heterozygous state in this patient. Despite extensive mutation analysis, no other potential disease-causing genetic alterations could be detected in the PPOX gene or the uroporphyrinogen III synthase gene. Slight overrepresentation of the mutant PPOX allele was however, observed repeatedly in dna of the proband compared to other R59W heterozygotes, including his mother who also tested positive for mutation R59W using restriction enzyme analysis and direct dna sequencing. Confirmation of this phenomenon by real-time polymerase chain reaction analysis and microsatellite analysis, using highly informative markers flanking the PPOX gene, raised the possibility of partial homozygosity for VP in this patient. This study represents the first report of overrepresentation of mutation R59W in a patient with a severe form of VP. A homozygote for the R59W mutation has never been detected, and the severe clinical manifestation observed in our patient is consistent with the hypothesis that such a genotype will not be compatible with life.- - - - - - - - - - ranking = 1keywords = abdominal pain (Clic here for more details about this article) |
2/2. Clinical indications for the investigation of porphyria: case examples and evolving laboratory approaches to its diagnosis in new zealand.patients with porphyria present in a diverse and unusual variety of ways and most clinicians will see only a few cases, if any, during their professional lives. Porphyria may present (1) with acute symptoms, which may be abdominal pain, neurological or psychiatric; (2) with skin rash or photosensitivity; or (3) with a putative family history. Screening for latent porphyria has been greatly facilitated by fluorescence emission scanning of plasma and by mutational analysis. Our reference laboratory has recently diagnosed several cases of the less common types of porphyria, which we postulate is due to the availability of these methods and to the changing population of new zealand. Accurate screening and diagnosis of porphyria is important, as an acute porphyric attack is life-threatening and preventable. Retrospective diagnosis may be difficult.- - - - - - - - - - ranking = 1keywords = abdominal pain (Clic here for more details about this article) |