The
porphyrias are inherited or acquired metabolic disorders caused by a partial deficiency in one of the
enzymes of the
heme biosynthetic pathway. Eight
enzymes are utilized in the synthesis of
heme. An
enzyme defect in one of the last seven
enzymes will result in one of the seven different forms of
porphyria, some of which have similar signs and symptoms. This article describes six diabetic, azotemic patients with no prior history of
porphyria, who developed a syndrome similar to
acute intermittent porphyria after initiation of treatment with
erythropoietin. One of the patients developed the syndrome predialysis, whereas the remaining patients were on maintenance
hemodialysis. The symptoms varied but all resolved when
erythropoietin was discontinued and reappeared in four cases when
erythropoietin was restarted. In all of the patients, the
enzyme aminolevulinic acid-dehydratase (ALA-D) was low and the uroporphyrinogen synthase was normal. This
enzyme abnormality suggests an acquired form of
delta-aminolevulinic acid dehydratase porphyria (
ADP). Lead toxicity,
succinylacetone, and
zinc deficiency are known to depress ALA-D, but these conditions were not present. The development of the
acute porphyria syndrome while the patients were receiving pharmacological doses of
erythropoietin, which resolved when the
drug was stopped, suggests that by stimulating
heme synthesis,
erythropoietin may unmask an
enzyme deficiency resulting in the clinical expression of
ADP. The patients responded favorably to a regimen that included discontinuation of
erythropoietin, tight
blood sugar control, maintaining the hematocrit above 30%, and a KT/V, a measure of dialysis adequacy, of 1.5 in the
hemodialysis group.
Plasmapheresis accelerated the recovery when used in two patients.