Page 571 - Hematology_ Basic Principles and Practice ( PDFDrive )

486 Part V Red Blood Cells

TABLE Hereditary Iron Overload Disorders
36.4
Gene, Plasma
Chromosome Transferrin
Disorder Location Inheritance Saturation Plasma Ferritin Iron Deposition Sites Clinical Manifestations
Hereditary HFE, 6p21 Autosomal Early increase; Later increase Parenchymal iron Liver and heart
hemochromatosis, recessive >45% after 3rd overload affecting disease, diabetes,
HFE-associated (type 1; decade of hepatocytes, heart, gonadal failure,
OMIM 235200) life pancreas, other arthritis, skin
organs pigmentation
Hereditary TFR2, 7q22 Autosomal Early increase; Later increase Parenchymal iron Liver and heart
hemochromatosis, recessive >45% after 3rd overload affecting disease, diabetes,
TfR2-associated (type decade of hepatocytes, heart, gonadal failure,
3; OMIM 604250) life pancreas, other arthritis, skin
organs pigmentation
Juvenile hemochromatosis, HJV, 1q21 Autosomal Early increase; Increased by Parenchymal iron As for hereditary
hemojuvelin-associated recessive >45% 2nd decade overload affecting hemochromatosis,
(type 2A; OMIM of life hepatocytes, heart, but liver
602390) pancreas, other involvement less
organs prominent
Juvenile hemochromatosis, HAMP, Autosomal Early increase; Increased by Parenchymal iron As for hereditary
hepcidin-associated 19q13 recessive >45% 2nd decade overload affecting hemochromatosis,
(type 2B; OMIM of life hepatocytes, heart, but liver
613313) pancreas, other involvement less
organs prominent
Hemochromatosis, SCL11A2, Autosomal Early increase; Normal to Hepatic iron overload, Severe microcytic
DMT1-associated 12q13 recessive >45% moderately predominantly in anemia, liver
(OMIM 206100) elevated hepatocytes dysfunction
Atransferrinemia (OMIM TF, 3q22 Autosomal No plasma Increased Parenchymal iron Transfusion-
209300) recessive transferrin overload affecting dependent
hepatocytes, heart, iron-deficiency
pancreas; no iron anemia, growth
stores in bone retardation, poor
marrow or spleen survival
Aceruloplasminemia CP, 3q24-q25 Autosomal Decreased Increased Marked iron Diabetes, progressive
(OMIM 604290) recessive accumulation in neurologic disease,
basal ganglia, retinal degeneration
liver, pancreas
Hemochromatosis, SLC40A1, Autosomal Remains Early increase Predominantly None
ferroportin-associated, 2q32 dominant normal or macrophage iron
with impaired iron low deposition
export (type 4A; OMIM
606069)
Hemochromatosis, SLC40A1, Autosomal Early increase; Early increase Parenchymal iron Similar to HFE-
ferroportin-associated, 2q32 dominant >45% overload affecting associated
with hepcidin hepatocytes, heart, hemochromatosis
resistance (type 4B; pancreas, other
OMIM 606069) organs

A B C
Fig. 36.4 HFE HEMOCHROMATOSIS. Liver biopsy sample from a 46-year-old man with homozygous
HFE hemochromatosis. Hematoxylin and eosin stain of the liver (A) shows intact hepatic architecture. Iron
stain (B–C) shows marked diffuse iron deposits in the hepatocytes throughout the lobules. A normal liver
would show essentially no iron in the hepatocytes.