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> From: Niels Erik Petersen <[log in to unmask]>
> To: [log in to unmask]
> Subject: RE: Puzzling porfyrin profile
> Date: Thursday, May 06, 1999 11:22 PM
>
> Patients who are genetically proned for acute porphyria probably rather
> often will have normal urinary excretion of prophyrines and
porphyrinogens
> outside attacks.
Many qualitative PBG assays are too insensitive to distinguish normal
from abnormal - use of resin based PBG methods
such as those described by J Buttery in Clinical Chemistry have improved
the analytical sensitivity of PBG measurement.
Certainly HCP and VP patients tend to have normal levels between attacks.
>We therefore believe, that a more reliable biochemically
> diagnosis would be obtained if enzyme-activity are measured - in the case
of
> acute intermittent porphyria ery-PBGD activity. Alternatively, analysis
of
> the relevant genes from the heme-synthesis pathway may give the
diagnosis.
> We offer you with pleasure to analyse the Porphobilinogen Deaminase
(acute
> intermittent porphyria) and Coproporphyrinogen Oxidase (hereditary
> coproporphyria) gene in DNA from this patient if you send us a DNA-sample
> (or just an EDTA-blood sample). Later this year, we expect to be able to
> offer you an analysis for mutations within the Protoporphyrinogen Oxidase
> gene (porphyria variegata) as well.
I am unaware of any laboratories offering this service as a routine in
Australia. I was under the impression that the mutations present in this
genes were heterogeneous and that to test for the carrier status of an
individual would require the determination of the specific gene mutation
present in the affected kindred. From a position of ignorance I would guess
that the assay of the ProtoOxidase and CoproOxidase gene would be easier
proposition than determination of activity of these mitachondrial enzyme.
The Royal Melbourne Hospital have been using a the faecal CI/CIII ratio as
a screening test for HCP for some time. Of interest, I believe the VP gene
mutation has been used in Australia to show that a cluster of Australian
Aboringes with VP found in Western Australian do not have the same mutation
as the South African VP mutation - the Dutch East India ships provisioned
in Capetown before navigating due east to toward the Australian coast
before heading north - sometimes they were shipwrecked here.
What advice do you give with a positive result considering the low
penetrance of these conditions? and considering the heterogeneity of the
mutations are you compelled to find the specific mutation in the index case
before being able to report a negative result?
I am not sure of the amount of 400 nm light in Denmark but are your VP
(and HCP) patients more likely to present with neurological symptoms rather
than skin symptoms?
>
> Regards
> Niels Erik Petersen
> Consultant, associate professor, PhD
> The Danish Porphyria Center
Michael Freemantle
Sullivan Nicolaides Pathology
PO Box 344
Indooroopilly Q4068
Brisbane
Australia 4068
ph +61 (0)7 33778638
fax +61 (0)7 38705989
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