Table 2.

Primary Iron Overload Disorders to Consider in the Differential Diagnosis of TFR2-Related Hemochromatosis

Gene(s)DisorderMOIFeatures of Disorder
Overlapping w/TFR2-HCDistinguishing from TFR2-HC
BMP6 BMP6-related iron overload (OMIM 620121)AD
  • Biochemical features of iron overload
  • Liver iron accumulation
  • Normal transferrin saturation in some
  • Mild-to-moderate late onset of iron overload
CP Aceruloplasminemia AR
  • Hyperferritinemia
  • Diabetes mellitus
  • Anemia
  • Iron deposition in hepatic reticuloendothelial (not parenchymal) cells
  • Brain iron accumulation manifesting as retinal degeneration & neurologic disease (movement disorders & ataxia)
HFE HFE-related hemochromatosis ARBiochemical & clinical features of iron overload
HAMP
HJV 		Juvenile hemochromatosis ARBiochemical & clinical features of iron overload
  • Earlier onset
  • More severe clinical manifestations, esp cardiomyopathy & hypogonadotropic hypogonadism
SLC40A1 SLC40A1-related hemochromatosis assoc w/gain-of-function pathogenic variants (OMIM 606069)ADBiochemical & clinical features of iron overloadLater-onset clinical manifestations of iron overload
SLC40A1-related hemochromatosis assoc w/loss-of-function pathogenic variants (OMIM 606069)ADHyperferritinemia
  • At early stage: anemia & low transferrin saturation
  • Iron deposition in hepatic reticuloendothelial (not parenchymal) cells
  • Reduced tolerance to phlebotomy

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; TFR2-HC = TFR2-related hemochromatosis

From: TFR2-Related Hemochromatosis

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