Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: a case report.

Abstract

BACKGROUND:

Hereditary hemochromatosis is a heterogenous group of inherited iron-overload conditions that is characterized by increased intestinal absorption and deposition in vital organs. Hepcidin is a soluble regulator that acts to attenuate both intestinal iron absorption and iron release from reticuloendothelial macrophages through internalization of ferroportin-1, an iron exporter. Ferroportin disease is hereditary hemochromatosis which is affected by SLC40A1, a gene coding ferroportin-1, and phenotypically classified into two forms (classical and nonclassical). In nonclassical form, ferroportin mutations are responsible for a gain of function with full iron export capability but insensitivity to downregulation by hepcidin. Here, we report a case of nonclassical ferroportin disease.

CASE PRESENTATION:

A 46-year-old Japanese man showed elevated serum iron (284 μg/dl), ferritin (1722 ng/ml), transferrin saturation ratio (91.3%), and hepcidin-25 level (139.6 ng/ml). Magnetic resonance imaging (MRI) demonstrated a marked reduction in the signal intensity of the liver in T1- and T2-weighted images. The liver histology exhibited a large amount of iron that had accumulated predominantly in hepatocytes. We identified a heterozygous 1520A > G (p.H507R) mutation in the SLC40A1 gene. Phlebotomy (400 ml at a time) was monthly performed for 3 years in this patient. Importantly, the serum hepcidin level (1.0 ng/ml) was normal when the serum ferritin level was normal and hepatic iron accumulation was remarkably reduced after 3 years of phlebotomy.

CONCLUSIONS:

The present case demonstrated for the first time that there was a correlation between hepatic iron levels as measured by MRI and serum hepcidin levels through long-term phlebotomy in a patient with ferroportin disease with the p.H507R mutation of in SLC40A1.

• Authors: Sohji Nishina, Yasuyuki Tomiyama, Katsuya Ikuta, Yasuaki Tatsumi, Yasumichi Toki, Ayako Kato, Koichi Kato, Naoko Yoshioka, Kyo Sasaki, Yuichi Hara, Keisuke Hino
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 21 Issue 1 Pg. 111 (Mar 05 2021) ISSN: 1471-230X [Electronic] England
• PMID: 33673803 (Publication Type: Case Reports, Journal Article)

Chemical References

• Cation Transport Proteins
• metal transporting protein 1
• Iron

Topics

• Cation Transport Proteins (genetics)
• Hemochromatosis (genetics, therapy)
• Humans
• Iron
• Male
• Middle Aged
• Mutation
• Phlebotomy