Appropriate Clinical Genetic Testing of Hemochromatosis Type 2-4, Including Ferroportin Disease

Devan S Kowdley; Kris V Kowdley

doi:10.2147/TACG.S269622

Appropriate Clinical Genetic Testing of Hemochromatosis Type 2-4, Including Ferroportin Disease

Appl Clin Genet. 2021 Aug 12:14:353-361. doi: 10.2147/TACG.S269622. eCollection 2021.

Authors

Devan S Kowdley¹, Kris V Kowdley¹

Affiliation

¹ Liver Institute Northwest and Elson S. Floyd College of Medicine, Washington State University, Seattle, WA, USA.

Abstract

Hereditary hemochromatosis (HH) is an inherited iron overload disorder due to a deficiency of hepcidin, or a failure of hepcidin to degrade ferroportin. The most common form of HH, Type 1 HH, is most commonly due to a homozygous C282Y mutation in HFE and is relatively well understood in significance and action; however, other rare forms of HH (Types 2-4) exist and are more difficult to identify and diagnose in clinical practice. In this review, we describe the clinical characteristics of HH Type 2-4 and the mutation patterns that have been described in these conditions. We also review the different methods for genetic testing available in clinical practice and a pragmatic approach to the patient with suspected non-HFE HH.

Keywords: HAMP; ferroportin disease; hemochromatosis; hepcidin; juvenile hemochromatosis; non-HFE; transferrin-receptor 2.

Publication types

Review