ORPHA: 79230; DO: 0111032;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19q13.12 | Hemochromatosis, type 2B | 613313 | Autosomal recessive | 3 | HAMP | 606464 |
A number sign (#) is used with this entry because this form of juvenile hemochromatosis (HFE2B) is caused by homozygous mutation in the HAMP gene (606464) on chromosome 19q13.
For a general phenotypic description and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200.
Juvenile, or type 2, hemochromatosis is an autosomal recessive inborn error of iron metabolism that leads to severe iron loading and organ failure before 30 years of age (summary by Roetto et al., 1999). HFE2B is caused by mutation in the HAMP gene (606464). HFE2 is genetically heterogeneous (see HFE2A, 602390).
Papanikolaou et al. (2002) reported a single inbred pedigree with juvenile hemochromatosis that was not linked to 1q. The 2 affected daughters of third-cousin parents had a typical JH phenotype.
Roetto et al. (2003) studied 2 families with juvenile hemochromatosis not linked to 1q, including the one studied by Papanikolaou et al. (2002). Using microsatellite markers encompassing a region of 2.7 cM on 19q13 in one family, they identified a region of homozygosity in both probands. They then sequenced the coding region of the HAMP gene (606464), exon-intron boundaries, and 5- and 3-prime untranslated regions in this family and a second family (one studied by Camaschella et al. (1997)) and identified 2 mutations (606464.0001, 606464.0002). All affected individuals were less than 30 years at onset of clinical symptoms and had severe iron overload with liver fibrosis or cirrhosis and hypogonadism, meeting the diagnostic criteria for juvenile hereditary hemochromatosis (De Gobbi et al., 2002). One affected individual also had cardiomyopathy.
Camaschella, C., Roetto, A., Cicilano, M., Pasquero, P., Bosio, S., Gubetta, L., Di Vito, F., Girelli, D., Totaro, A., Carella, M., Grifa, A., Gasparini, P. Juvenile and adult hemochromatosis are distinct genetic disorders. Europ. J. Hum. Genet. 5: 371-375, 1997. [PubMed: 9450181]
De Gobbi, M., Roetto, A., Piperno, A., Mariani, R., Alberti, F., Papanikolaou, G., Politou, M., Lockitch, G., Girelli, D., Fargion, S., Cox, T. M., Gasparini, P., Cazzola, M., Camaschella, C. Natural history of juvenile haemochromatosis. Brit. J. Haemat. 117: 973-979, 2002. [PubMed: 12060140] [Full Text: https://doi.org/10.1046/j.1365-2141.2002.03509.x]
Papanikolaou, G., Papaioannou, M., Politou, M., Vavatsi, N., Kioumi, A., Tsiatsiou, P., Marinaki, P., Loukopoulos, D., Christakis, J. I. Genetic heterogeneity underlies juvenile hemochromatosis phenotype: analysis of three families of northern Greek origin. Blood Cells Molec. Dis. 29: 168-173, 2002. [PubMed: 12490283] [Full Text: https://doi.org/10.1006/bcmd.2002.0553]
Roetto, A., Papanikolaou, G., Politou, M., Alberti, F., Girelli, D., Christakis, J., Loukopoulos, D., Camaschella, C. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nature Genet. 33: 21-22, 2003. [PubMed: 12469120] [Full Text: https://doi.org/10.1038/ng1053]
Roetto, A., Totaro, A., Cazzola, M., Cicilano, M., Bosio, S., D'Ascola, G., Carella, M., Zelante, L., Kelly, A. L., Cox, T. M., Gasparini, P., Camaschella, C. Juvenile hemochromatosis locus maps to chromosome 1q. Am. J. Hum. Genet. 64: 1388-1393, 1999. [PubMed: 10205270] [Full Text: https://doi.org/10.1086/302379]