Hereditary hemochromatosis

type 1 (HFE Related)

Rizky Amalia Siregar

Magister Biomedik FK USU
2018
 Definisi
• Gangguan yang menyebabkan tubuh
menyerap terlalu banyak zat besi dari
makanan, yang disebabkan oleh adanya
mutasi di gen HFE di kromosom 6.

Other names for this gene

• hemochromatosis
• hemochromatosis, genetic; GH
• Hemochromatosis, Hereditary; HH
• Hereditary hemochromatosis protein
• HFE_HUMAN
• HLA-H antigen
Kromosom 6
-170 juta pasang basa
- 5,5-6% dari total DNA dalam sel
P- arm
Q-arm
 Hereditary hemochromatosis types
HH Tipe 1 HH Tipe 2
• Gene : HFE • Gene :
• Kromosom : 6 (6p22.2) - Tipe 2A: HFE2 (HJV)
• Produk protein : HFE protein Kromosom : 1 (1q21)
• Fungsi : Mengatur penyerapan zat besi 
Produk protein : Hemojuvelin
regulasi interaksi reseptor transferin dengan
transferrin - Tipe 2B: HAMP
Kromosom: 19 (19q13)
• Manifestasi Klinis: Produk protein: Hepsidin
• iron overload leads to multipleorgan damage Fungsi: Regulasi hepsidin
such as :
– liver cirrhosis, • Manifestasi Klinis :
– cardiomyopathy,
– severe iron overload usually associated
– diabetes, with:
– arthritis,
– liver damage,
– hypogonadism
– cardiomyopathy
– skin pigmentation
– hypogonadotrophic hypogonadism
Symptoms typically begin between the ages
of 40-60 years-old People with hemochromatosis type 2 may
have heart disease by age 30
HH Tipe 3
• Gene : TFR 2
• Kromosom: 7 (7q22.1)
• Produk protein : Transferrin reseptor 2
• Fungsi : Membantu besi masuk ke sel hati
(hepatosit)
• Manifestasi Klinis:
• Similiar to HFE hemochromatosis
– abnormal liver function,
– diabetes,
– hypogonadism,
– cardiomyopathy and arthritis
Symptoms of hemochromatosis type 3
typically begin before 30-years-old
HH Tipe 4
• Gene : SLC40A1
• Kromosom: 32 (2q32.2)
• Produk protein : ferroportin
• Fungsi : Membantu besi masuk ke sel hati
(hepatosit)
• Manifestasi Klinis :
– typically present with low to normal
transferrin saturation
– iron overload within macrophages, mainly
from the liver, spleen and bone marrow.
– mild irondeficient anemia
Symptoms of hemochromatosis type 4 can
begin anytime from childhood to
adulthood
 Mutation

-G-to-A missense mutation leading to the

substitution of tyrosine for cysteine at
amino acid position 282 of the protein
product (C282Y)

There are two other regularly

identified mutations,
- which aspartate is substituted for
histidine at amino acid position 63 (H63D),
- the other in which cysteine is substituted
for serine at amino acid position 65 (S65C).
 Inheritance pattern

• Types 1, 2, and 3 hemochromatosis are inherited in an autosomal recessive pattern

• Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern
Treatment
Thank You