Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox

Abstract

Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g.47G>A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 μmol/g; reference value < 36 μmol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.

Clinical practice guidelines on hemochromatosis: Asian Pacific Association for the Study of the Liver

“…It is rare and falls under the classification of non-HFE-hemochromatosis. It can be caused by homozygous mutations in HJV or HAMP, which both result in loss of production of hepcidin and subsequent iron overload [ 152 , 153 ]. It is best managed by early diagnosis and phlebotomy therapy to reduce body iron stores [ 5 ].…”

Haemochromatosis revisited

“…The adequate content of body iron requires the maintenance of plasma iron concentration within normal limits (12-25 μM) and the regulation of TS. Normal TS is between 20% and 45%, allowing adequate iron delivery to the cells[ 18 ]. In mammals, plasma iron binds to transferrin that is synthetized by the hepatocytes and, once released in the plasma, receives two atoms of ferric iron by an active process involving ferroxidase enzymes.…”