SERUM FERRITIN AS A POSSIBLE MARKER OF THE HEMOCHROMATOSIS ALLELE

To determine whether a correlation exists between the biochemical expression of hemochromatosis and the HLA genotype, we studied 174 family members of 32 persons with the disease. Persons who shared both HLA haplotypes with the proband (and presumably having two hemochromatosis alleles) differed significantly from those who shared only one haplotype (and presumably having one hemochromatosis allele) in terms of serum iron (P<0.001 for both sexes), unsaturated iron-binding capacity (P<0.01 for female and P<0.0001 for male subjects) and serum ferritin (P<0.0001 for female and P<0.00001 for male subjects). The only significant difference between relatives having one hemochromatosis allele and age and sex-matched controls was related to serum ferritin values in male subjects (P<0.05, despite considerable overlap). In our hands, serum ferritin was the best indicator of disordered iron metabolism and was elevated among most homozygous but among few heterozygous family members. (N Engl J Med 301:169–174, 1979) IDIOPATHIC hemochromatosis is determined by a locus closely linked to the A locus of the HLA complex on chromosome 6.1,2 The disease becomes clinically manifest in patients homozygous for the predisposing allele3,4 indicating a recessive mode of inheritance, as already suggested by phenotypic studies.5,6 The hypothesis implicating two different loci on chromosome 6 in the development of hemochromatosis7 seems highly improbable.8 The pattern of transmission of the predisposing alleles in a pedigree can be traced by typing for the A and B alleles of the HLA complex, which are carried on the same chromosome and form the following haplotype: hemochromatosis. © 1979, Massachusetts Medical Society. All rights reserved.