The Ferrochelatase Deficiency (Fechm1Pas) Mutation, Chromosome 18

The ferrochelatase deficiency mutation was mapped to mouse Chromosome 18, 40 cM from the centromere (Montagutelli, unpublished). Very severe liver lesions are observed in homozygous ferrochelatase deficiency mutant mice. At 15 days of age, there is a 65% increase in the liver to total body weight ratio. Protoporphyrin levels are also considerably elevated in erythrocytes (25-fold), plasma (20to 200-fold), liver (1000-fold), and stool (10-fold). Serum alkaline phosphatase and transaminases are consistently increased as a consequence of chronic liver damage. Enzymatic activity of ferrochelatase in spleen, kidney, and liver in homozygotes is 3 to 7% of normal controls and close to 50% of normal in heterozygotes. Fatalities from rapidly progressive liver disease have been reported in at least 20 patients, which is an indication for liver transplantation. The ferrochelatase deficiency mutation is the first murine genetically determined model for human erythropoietic protoporphyria.