Porphyria Educational Services
PORPHYRIA EDUCATIONALSERVICES BULLETIN
Vol. 1 No. 45
October 31, 1999
FOCUS: A Variant Form of Acute Intermittent
Porphyria
For a diagnosis of most acute intermittent porphyria, a confirmed
diagnosis comes by the positive 24 hour quanitative urine testing
and a red blood cell tests showibng a marked decreased in the PBG-deaminase.
However in 1981 Dr. P. Mustajoki suggested that in one variant of
acute intermittent porphyria the enzyme defect is not expressed
in red cells. Dr. Mustajoki studied a large family in which 10
members had AIP with the normal erythrocyte PBG-deaminase
activity. Forty-nine other patients with AIP who were unrelated
to this kindred had the usual low activity of PBG-deaminase.
Generally, however, reduced activity of this enzyme in red cells
is a consistent finding during or between acute attacks, and
characterizes latent AIP that is inherited as an autosomal
dominant trait. More on this can be found in writings by Dr.
Shigeri Sassa and others in 1974 as well as Dr. Kreimer-Birnbaum,
in 1975.
While the initial study was undertaken in northern Europe, the
finding of this variant form of acute intermittent porphyria is
not limited to the northern reaches of Europe has has been
documented within the United States and in families living on the
west coast of England.
Most enzymopathies are recessively inherited because few enzymes
are so rate-limiting as to cause a serious reduction in the rate
of a metabolic pathway when the enzyme has 40 to 60% normal
activity.
So how does this this variant form of AIP show up in genetic
coding?
Genetic mapping for my family looks like this:ALA enzyme
AIP syndrome Inheritance pattern AB Location 9q
glutamine for arginate mutation at 168 or position 173 arg 167 -to-gin
Chromosome 11q 24.1-1q 24.2 Dominant Exon 10.
There are new variants being found all the time in the difference
forms of porphyria. As one researcher stated it: "We
are only now at the tip of the iceberg. We have many miles
to go and lots of discovers to make where'porphyria is concerned."