- Many South African patients with `MS or a
partially expressed form of the disease have been misdiagnosed with
porphyria (supported by preliminary data), partly due to the fact that
VP is common in South Africa (due to a founder effect and possibly also
chronic sun exposure) and `MS considered to be uncommon in this country.
- Iron levels required for heme synthesis are
frequently reduced in a subgroup of `MS patients due to a genetic
defect associated with iron metabolism, so that the heme biosynthesis
pathway is affected, thereby mediating CNS damage in a manner similar
to that observed in the acute porphyrias. The accumulated CNS damage
from years of repetition of this process eventually results in
disability.
- The increased prevalence of `MS in women compared
with men is due to genetic defects of iron metabolism and/or the effect
of sex hormones on the heme biosynthesis pathway in subjects with a
predisposition for MS
- The CNS damage is evoked by a disproportion
between the porphyrin precursors delta aminolevulinic acid and
porphobilinogen (reducing agents) and uroporphyrin-1 isomers
(antioxidants). Uroporphyrin-1 is deficient as a result of iron
deficiency, leaving the CNS vulnerable to the oxidative damage of the
precursors.
- The neurotoxic process causing central nervous
system (CNS) damage in MS patients with intermittent iron deficiency
due to a genetic defect may also occur in persons who become anemic for
other reasons. This may provoke onset of autoimmune `MS as the immune
system may mistakenly target CNS components like myelin as it attempts
to clear the damage left behind by this process. Characterization of
the putative HBMS gene and its product may therefore also explain the
establishment of classical MS.
