Therapeutic recommendations in HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype

Abstract

Although guidelines are available for hereditary hemochromatosis, a high percentage of the recommendations within them are not shared between the different guidelines. Our main aim is to provide an objective, simple, brief, and practical set of recommendations about therapeutic aspects of HFE hemochromatosis for p.Cys282Tyr (C282Y/C282Y) homozygous genotype, based on the published scientific studies and guidelines, in a form that is reasonably comprehensible to patients and people without medical training. This final version was approved at the Hemochromatosis International meeting on 12th May 2017 in Los Angeles.

Non-HFE mutations in haemochromatosis in China: combination of heterozygous mutations involving HJV signal peptide variants

“…Our results indicate that the compound heterozygous mutations of HJV or combined heterozygous mutations of BMP/SMAD pathway genes, marked by HJV variants in the signal peptide region, may constitute a major aetiological factor for HH in China. Notably, independently of identified mutation, the patient with haemochromatosis must be treated by phlebotomy or chelation therapy when phlebotomies are medically contraindicated according to recently published guidelines 29. It would be more helpful if we have specific recommendations for patients with non- HFE haemochromatosis in the future.…”

Diagnosis and management of hereditary haemochromatosis

“…Because serum iron levels are dynamic, with diurnal and dietary fluctuations, clinicians should attempt to standardize the timing of TS to obtain consistent levels during the HH work up. Multiple TS levels above 45%, in conjunction with elevated SF, indicate the need for genetic testing for haemochromatosis .…”

“…The management of HH has remained unchanged for many decades and includes prevention and treatment of iron overload through phlebotomy. Phlebotomy is a straightforward and effective method of reducing total body iron stores and has been shown to improve survival and prevent many of the long‐term complications of iron deposition . Phlebotomy is generally safe and well tolerated, and remains the therapy of choice for those with iron overload.…”

“…Recent guidelines recommend that patients with HFE C282Y homozygosity and biochemical evidence of iron overload (SF >300 ng/ml in males, >200 ng/ml in females, and fasting TS >45%) should start phlebotomy . The induction phase of phlebotomy should remove 400–500 mL, or one unit, of whole blood every 1–2 weeks, depending on patient tolerance, with the goal of achieve a serum ferritin <50 ng/ml . One unit of phlebotomized blood contains between 200–250 mg of iron .…”

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

“…Early diagnosis and iron depletion therapy has the potential of improving the survival rate of patients [9] . HH is readily treated by venesection therapy, which is very efficient in removing excess iron and involves two successive treatment phases [116] . In the initial induction phase, the excess iron present at the time of diagnosis is removed by 1-2 weekly venesections (7.5 mL/kg body weight per venesection).…”