Impaired heme synthesis in a family with Pelger-Huët anomaly, recurrent abdominal pain attacks and impaired neutrophil motility in vitro.

Abstract

Heme synthesis was studied by measuring the activity of delta-aminolevulinic acid synthase (AmLev synthase) in granulocytes, the activity of delta-aminolevulinic acid dehydratase (AmLev dehydratase) and of uroporphyrinogen I synthase in erythrocytes as well as the concentrations of coproporphyrin and protoporphyrin in erythrocytes of 6 patients with Pelger-Huët anomaly. 3 of these patients from the same kindred had a syndrome of recurrent attacks of fever and abdominal pains, a tendency to skin infections, delayed wound healing and impaired neutrophil motility. The other 3 patients were asymptomatic. The activity of AmLev synthase was depressed in all 3 symptomatic patients and normal in the asymptomatic patients. 1 symptomatic patient had a decreased erythrocyte protoporphyrin concentration. These findings indicate a derangement of heme synthesis in the symptomatic patients. Their abdominal pain attacks could be due to heme depletion. The findings suggest that the abdominal pains of patients with porphyria could be due to decreased heme synthesis rather than due to accumulation of porphyrin precursors in tissues. The cause of the impaired neutrophil motility may be a defect in energy metabolism due to decreased supply of heme for oxidative metabolism.