Elder GH, Whatley SD, Woolf J, Mason NG, 1Masters G, Badminton MN

Departments of Medical Biochemistry and Immunology and 1Haematology, University Hospital of Wales and School of Medicine, Cardiff University, Cardiff

Rare patients have been reported in whom the late onset of an erythropoietic porphyria has occurred in association with the preleukaemic disorders, myelodysplasia (MDS) and myeloproliferative disorder. We have investigated 4 patients aged over 40 years who developed cutaneous porphyria and overproduction of uroporphyrin I and coproporphyrin I, in a pattern typical of congenital erythropoietic porphyria (CEP), in association with MDS or myelofibrosis.

Findings in these patients have been compared with those in patients with classical CEP. Features distinguishing the 4 patients with late-onset disease from classical CEP were haemorrhagic bullae and thrombocytopenia, lower erythrocyte porphyrin concentrations (mean 4.2 µmol/L vs. 17.5 µmol/L), normal erythrocyte uroporphyrinogen III synthase (UROS) activity, and absence of mutations in the UROS gene in germline DNA. Examination of bone marrow aspirates showed porphyrin fluorescence in some erythroid cells. No abnormalities of chromosome 10 were detected by conventional bone marrow cytogenetics. No UROS mutation was identified by sequencing DNA extracted from unfractionated bone marrow. Only a minority of erythroid blast forming units cultured from peripheral blood showed porphyrin fluorescence, indicating that porphyrin overproduction was restricted to a minor clone of  erythropoietic cells. These observations characterize the form of late-onset erythropoietic porphyria associated with preleukaemic disorders as a distinct syndrome, analogous to other disorders, such as the α-thalassaemia-myelodysplastic syndrome, in which a normally inherited condition arises in association with MDS. Like them it is probably caused by expansion of a clone of haematopoietic cells containing an acquired somatic mutation that has arisen as a consequence of the genomic instability that is one of the characteristic features of these haematological disorders.