Table 2 Overview of characteristics of... | American Society of Hematology

Table 2

Overview of characteristics of rare microcytic anemias due to genetic disorders of iron metabolism or heme synthesis

Pathophysiology	Low iron availability for erythropoiesis			Defect in iron acquisition of erythroid progenitor cells			Defect in heme synthesis or Fe-S cluster biogenesis
Disorder	IRIDA	Ferroportin disease*	ACP	Hypotransferrinemia	Microcytic anemia with iron loading	Sideroblastic anemia	Sideroblastic anemia	XLSA with ataxia	XLSA	Sideroblastic anemia	EPP		CEP
Disorder	IRIDA	Ferroportin disease*	ACP	Hypotransferrinemia	Microcytic anemia with iron loading	Sideroblastic anemia	Sideroblastic anemia	XLSA with ataxia	XLSA	Sideroblastic anemia	EPP	XLDPP	CEP	XLCEP
Gene	TMPRSS6	SLC40A1	CP	TF	DMT1	STEAP3	SLC25A38	ABCB7	ALAS2†	GLRX5	FECH	ALAS2‡	UROS	GATA1
Protein	Matriptase-2	Ferroportin-1	CP	Transferrin	DMT1	STEAP3	SLC25A38	ABCB7	ALAS2	GLRX5	FECH	ALAS2	UROS	GATA1
Patients described (n)	20-100	>200	20-100	5-20	5-20	<5 (n = 3)	20-100	5-20	>100	<5 (n = 1)	>100	20-100	>200	1
Inheritance	AR§	AD	AR/AD	AR	AR	AR/AD\|\|	AR	XL¶	XL	AR	Mostly AD	XL	AR	XL
Age at presentation	Child	Adult	40-50 y	Variable	Child	Child	Child	Child	Variable	Adult	Neonate/child	Neonate/ child	Variable, fetus-adult	Neonate
Neurologic symptoms	No	No	Yes	No	No	No#	No	Yes**	No	No	No	No	No	No
Skin symptoms	No	No	No	No	No	No	No	No	No	No	Yes	Yes	Yes	Yes
Anemia	Variable	Mild in 10%††	Mild	Variable	Variable	Variable	Severe	Mild	Mild, no anemia‡‡	Mild	Mild, no anemia	Mild, no anemia	Hemolytic, variable severity	Severe, hemolytic
MCV	Microcytic	Normocytic	Microcytic/normocytic	Microcytic	Microcytic	Microcytic/normocytica	Microcytic	Microcytic	Microcytic	Microcytic	Microcytic/normocytic	Normocytic	No data	Microcytic
Ring sideroblasts	No	No	No	No	No	Yes	Yes	Yes	Yes	Yes	Yes	No data	No	No
Iron loading	No	Yes	Yes	Yes	Variableb	Possiblec	Yes	No	Variable	Yes	No	No	No data	No
Ferritin	Normal-low	High	High	High	Variableb	Highc	High	Normal	Variable	High	Low/normal	Low/normal	No data	Normal
TSAT	<10%	Normal/ high††	Normal/low	100%	High	High	High	Normal	Normal/high	High	Normal/low	Normal/low	No data	Normal
Hepcidin	Highd	Variable	No data	Low	Normal/low	Normal/increasede	No data	No data	No data	No data	No data	No data	No data	No data
Treatment	Oral iron, intravenous iron, EPOf	Phlebotomy††	Chelation	Erythrocyte transfusion, apotransferrin, plasma, chelation, phlebotomy	Oral iron, erythrocyte transfusion, EPO, chelation	Erythrocyte transfusion, EPO chelation	HSCT, transfusion, chelation	Not indicated	Pyridoxine, folate, phlebotomy, chelation	Erythrocyte transfusion, chelation	No treatment of anemia, avoid light on skin	No treatment of anemia, avoid light on skin	HSCT, erythrocyte transfusion, chelation, avoid light on skin	No data

Pathophysiology	Low iron availability for erythropoiesis			Defect in iron acquisition of erythroid progenitor cells			Defect in heme synthesis or Fe-S cluster biogenesis
Disorder	IRIDA	Ferroportin disease*	ACP	Hypotransferrinemia	Microcytic anemia with iron loading	Sideroblastic anemia	Sideroblastic anemia	XLSA with ataxia	XLSA	Sideroblastic anemia	EPP		CEP
Disorder	IRIDA	Ferroportin disease*	ACP	Hypotransferrinemia	Microcytic anemia with iron loading	Sideroblastic anemia	Sideroblastic anemia	XLSA with ataxia	XLSA	Sideroblastic anemia	EPP	XLDPP	CEP	XLCEP
Gene	TMPRSS6	SLC40A1	CP	TF	DMT1	STEAP3	SLC25A38	ABCB7	ALAS2†	GLRX5	FECH	ALAS2‡	UROS	GATA1
Protein	Matriptase-2	Ferroportin-1	CP	Transferrin	DMT1	STEAP3	SLC25A38	ABCB7	ALAS2	GLRX5	FECH	ALAS2	UROS	GATA1
Patients described (n)	20-100	>200	20-100	5-20	5-20	<5 (n = 3)	20-100	5-20	>100	<5 (n = 1)	>100	20-100	>200	1
Inheritance	AR§	AD	AR/AD	AR	AR	AR/AD\|\|	AR	XL¶	XL	AR	Mostly AD	XL	AR	XL
Age at presentation	Child	Adult	40-50 y	Variable	Child	Child	Child	Child	Variable	Adult	Neonate/child	Neonate/ child	Variable, fetus-adult	Neonate
Neurologic symptoms	No	No	Yes	No	No	No#	No	Yes**	No	No	No	No	No	No
Skin symptoms	No	No	No	No	No	No	No	No	No	No	Yes	Yes	Yes	Yes
Anemia	Variable	Mild in 10%††	Mild	Variable	Variable	Variable	Severe	Mild	Mild, no anemia‡‡	Mild	Mild, no anemia	Mild, no anemia	Hemolytic, variable severity	Severe, hemolytic
MCV	Microcytic	Normocytic	Microcytic/normocytic	Microcytic	Microcytic	Microcytic/normocytica	Microcytic	Microcytic	Microcytic	Microcytic	Microcytic/normocytic	Normocytic	No data	Microcytic
Ring sideroblasts	No	No	No	No	No	Yes	Yes	Yes	Yes	Yes	Yes	No data	No	No
Iron loading	No	Yes	Yes	Yes	Variableb	Possiblec	Yes	No	Variable	Yes	No	No	No data	No
Ferritin	Normal-low	High	High	High	Variableb	Highc	High	Normal	Variable	High	Low/normal	Low/normal	No data	Normal
TSAT	<10%	Normal/ high††	Normal/low	100%	High	High	High	Normal	Normal/high	High	Normal/low	Normal/low	No data	Normal
Hepcidin	Highd	Variable	No data	Low	Normal/low	Normal/increasede	No data	No data	No data	No data	No data	No data	No data	No data
Treatment	Oral iron, intravenous iron, EPOf	Phlebotomy††	Chelation	Erythrocyte transfusion, apotransferrin, plasma, chelation, phlebotomy	Oral iron, erythrocyte transfusion, EPO, chelation	Erythrocyte transfusion, EPO chelation	HSCT, transfusion, chelation	Not indicated	Pyridoxine, folate, phlebotomy, chelation	Erythrocyte transfusion, chelation	No treatment of anemia, avoid light on skin	No treatment of anemia, avoid light on skin	HSCT, erythrocyte transfusion, chelation, avoid light on skin	No data

AD, autosomal dominant; AR, autosomal recessive; HSCT, hematopoietic stem cell transplantation; XL, X-linked.

Both LOF and GOF have been described; data in column reflect those of the combined group unless stated otherwise.

†

LOF.

‡

GOF.

Autosomal dominant inheritance pattern also described.

Heterozygous pathogenic mutation in combination with decreased expression of normal allele.

In some families, only women are affected because the defect is lethal in men.

Gonadal dysfunction.

Neurologic symptoms manifest in childhood; anemia may develop later in life (young adolescent).

††

In case of LOF mutations, anemia is more likely to occur and TSAT is lower.

‡‡

Anemia resolves by pyridoxine treatment in most XLSA patients.

Mean corpuscular Hb decreased.

Liver iron loading has been described and demonstrated by MRI and liver biopsy, even if serum ferritin is normal.

Iron loading may be secondary to erythrocyte transfusion.

Hepcidin:TSAT ratio is greater than the upper limit of the reference range in the absence of inflammation.

Measured after treatment with transfusions.

Only 1 human study available on EPO.

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