BIOCHEMICAL AND GENETIC CHARACTERIZATION OF FOUR CASES OF HEREDITARY COPROPORPHYRIA IN SPAIN
Carmen Herrero , Jordi To-Figueras , Celia Badenas , Maria T Enríquez (*), Sonia Segura , Concepción Alvarez (**), Montserrat Milà , Marius Lecha
Porphyria , Dermatology and Genetics Unit. Hospital Clínic. University of Barcelona. Villarroel 170. 08036 Barcelona. Spain; (*): Pediatrics Service. Hospital Axarquia. Malaga; (**): Hospital Marques de Valdecilla. Santander. Spain
Hereditary coproporphyria (HCP) is a rare disease that results from the inheritance of mutations in the CPO gene that encodes the mitochondrial enzyme, coproporphyrinogen oxidase. We report four cases of HCP in Spain. The initial biochemical analyses showed in all cases an increased excretion of fecal coproporphyrin and an inverted isomeric ratio (I:III < 1). Two of the patients showed increased urinary excretion of heme precursors porphobilinogen (PBG) and aminolevulinic acid (ALA) at the moment of the diagnosis and were treated with heme arginate. The other two, including a patient with the highest excretion of coproporphyrin III, showed PBG and ALA within normal limits at the moment of the diagnosis and during the follow-up. The existence of patients with a highly increased coproporphyrin accumulation and consistently low PBG and ALA over the time, suggests a complex mechanistic interdependence between both phenomena. The biochemical HCP profile was confirmed by a molecular analysis of the CPO gene that revealed the existence in three cases of novel mutations : V135A (404T>C; exon 1); L214R (641T>G, exon 2) and P249R (746C>G; exon 3) and in a fourth case of a previously described R426X mutation (1276C>T) in exon 6. Further biochemical (ratio coproporphyrin III:I in feces) and genetic analyses allowed to detect several non-symptomatic carriers among the close relatives. This is the first study to report a full biochemical and genetic characterization of HCP cases in Spain. (supported by grant FIS/03/ 0489/Spain).