© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, CIO Maternal Fetal Medicine, Prenatal Diagnosis and Biotech/Life Sciences Consultant, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Hemochromatosis is a hereditary disease in which the body absorbs excessive amounts of iron which deposits in various organs which can lead to:

  • Diabetes
  • Liver damage
  • Heart damage
  • Joint problems
  • Increased pigmentation of the skin

The diagnosis is often delayed until an individual’s middle years when organ damage had already occurred.

Hemochromatosis may occur in the neonatal period and occasionally may be acquired due to:

  • Chronic liver disease
  • Infection
  • Chronic anemia
  • Excessive iron ingestion or administration

There are 4 types of Hemochromatosis. Type 1, Type 2 and Type 3 are inherited in an autosomal recessive manner.

Type 1 Hemochromatosis occurs when an individual inherits one deleterious (disease causing) mutation from each parent who is a carrier and usually asymptomatic.

  • All children of two carrier parents have a 1:4 (25%) risk of inheriting one deleterious mutation from each parent and are affected
  • A 1:4 (25%) risk of inheriting neither deleterious mutation and being unaffected and a non-carrier
  • A 50% risk for inheriting one deleterious mutation from one parent and being a carrier.

Type 1 is due to a deleterious mutation in the HFE gene on chromosome 6p21.3.

Type 2 Hemochromatosis is also inherited in an autosomal recessive manner and is due to inheriting one deleterious mutation either in the HFE gene or the HAMP gene on chromosome m19q13.1. Type 2 usually begins in childhood.

Type 3 Hemochromatosis is inherited in an autosomal recessive manner and is due to inheritance of one deleterious mutation from each parent in the TFR2 gene on chromosome 7q22.

Type 4 Hemochromatosis also called (Ferroportin Disease) is inherited in an autosomal dominant manner (50%) if one deleterious gene is inherited from either parent or from a spontaneous mutation.  The incidence of the disease due to a spontaneous mutation is not known.  Type 4 is due to mutations in the SLC40A1 gene on chromosome 2q32.

If serum ferritin which is elevated in Hemochromatosis is less than 1000 ng/ml, survival rates are usually normal and the risks are low:

  • Severe liver damage
  • Cirrhosis of the liver
  • The risk for development of cancer due to elevated iron levels

Mutational analysis is available commercially.