X-linked sideroblastic anemia

A hereditary X-linked recessive sideroblastic anemia with variable age of onset and severity. It is characterized by (1) hypochromic microcytic anemia with microcytic and normocytic populations of RED BLOOD CELLS, (2) marrow ringed sideroblasts, particularly prominent in the late erythroid precursors, (3) a variable hematologic response to pharmacologic doses of PYRIDOXINE, and (4) systemic iron overload secondary to chronic ineffective ERYTHROPOIESIS. Mutations in the ALAS2 gene have been identified. OMIM: 300751

Also Known As:

Networked: 91 relevant articles (0 outcomes, 1 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Ataxia (Dyssynergia)
2.	Sideroblastic Anemia
3.	Friedreich Ataxia (Friedreich's Ataxia)
4.	Iron Overload
5.	sideroblastic spinocerebellar ataxia Anemia

Experts

1.	Harigae, Hideo: 11 articles (01/2022 - 06/2003)
2.	Fujiwara, Tohru: 7 articles (01/2022 - 01/2013)
3.	Puy, Hervé: 4 articles (11/2019 - 09/2008)
4.	Bishop, David F: 4 articles (01/2019 - 12/2002)
5.	Fleming, Mark D: 4 articles (10/2016 - 10/2002)
6.	Furuyama, Kazumichi: 4 articles (01/2013 - 06/2003)
7.	Gouya, Laurent: 3 articles (11/2019 - 09/2008)
8.	Ferreira, Gloria C: 3 articles (01/2017 - 11/2011)
9.	Bottomley, Sylvia S: 3 articles (10/2016 - 04/2003)
10.	Campagna, Dean R: 3 articles (10/2016 - 04/2007)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to X-linked sideroblastic anemia:

1.	Pyridoxine (Pyridoxin)FDA LinkGeneric 05/01/2017 - "A Novel ALAS2 Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked Sideroblastic Anemia." 10/01/2004 - "We report the case of a 40-year female who manifested late onset, pyridoxine-refractory X-linked sideroblastic anemia, heterozygous for the first described frameshift ALAS2 mutation, CD506-507 (-C). " 04/01/1995 - "We have studied a large kindred with a pyridoxine-sensitive form of X-linked sideroblastic anemia. " 03/01/1994 - "Pyridoxine-refractory congenital sideroblastic anaemia with evidence for autosomal inheritance: exclusion of linkage to ALAS2 at Xp11.21 by polymorphism analysis." 12/01/1994 - "Management decisions in relation to pyridoxine treatment, iron reduction, family studies, genetic counselling and antenatal diagnosis have in recent years become of practical relevance to families with known cases of congenital sideroblastic anaemia and careful documentation of the clinical outcome of these cases and of other family members is invaluable. "
2.	IronIBA 08/01/1983 - "The relationship between body iron status, degree of anaemia, erythroid expansion, age and sex has been studied in eight patients with congenital dyserythropoietic anaemia (CDA) and two patients with congenital sideroblastic anaemia, who had received no or very few blood transfusions and no medicinal iron during the course of their illness. " 06/01/2011 - "X-linked Sideroblastic Anemia (XLSA) is the most common genetic form of sideroblastic anemia, a heterogeneous group of disorders characterized by iron deposits in the mitochondria of erythroid precursors. " 12/01/1994 - "Management decisions in relation to pyridoxine treatment, iron reduction, family studies, genetic counselling and antenatal diagnosis have in recent years become of practical relevance to families with known cases of congenital sideroblastic anaemia and careful documentation of the clinical outcome of these cases and of other family members is invaluable. " 11/01/2011 - "Mutations that down-regulate activity can lead to X-linked sideroblastic anemia, which is characterized by abnormally high iron levels in mitochondria, while mutations that up-regulate activity are associated with X-linked dominant protoporphyria, which in contrast is phenotypically identified by abnormally high porphyrin levels. " 05/07/1977 - "The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. "
3.	5-Aminolevulinate SynthetaseIBA 01/01/2017 - "The first intronic mutations in the intron 1 GATA site (int-1-GATA) of 5-aminolevulinate synthase 2 (ALAS2) have been identified in X-linked sideroblastic anemia (XLSA) pedigrees, strongly suggesting it could be causal mutations of XLSA. " 10/01/2004 - "X-linked sideroblastic anemia (XLSA) is caused by mutations of erythroid-specific 5-aminolevulinate synthetase (ALAS2) gene. " 07/15/2003 - "X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). " 07/15/2003 - "A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia." 06/01/2003 - "X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). "
4.	Heme (Haem)IBA 09/17/2010 - "This case report describes a case of congenital sideroblastic anaemia, one of the prototype disorders of erythroid haem biosynthesis. " 05/01/2016 - "X-linked sideroblastic anemia (XLSA) is a disorder characterized by decreased heme synthesis and mitochondrial iron overload with ringed sideroblasts in bone marrow. " 02/01/2015 - "Herein, we focus on recent understanding of the heme biosynthetic pathway and on human disorders due to defective heme synthesis in erythroid cells, such as X-linked sideroblastic anemia and erythropoietic protoporphyria. " 10/01/2002 - "Initially, mutations in ALAS2 in X-linked sideroblastic anemia (XLSA) focused attention on the heme biosynthetic pathway as a primary cause of sideroblastic anemia. " 04/01/2013 - "The biosynthetic pathway for heme and key regulatory features are reviewed herein, along with specific human genetic disorders that arise from defective heme synthesis such as X-linked sideroblastic anemia and erythropoietic protoporphyria."
5.	EnzymesIBA 01/01/2022 - "Debilitating and painful diseases such as X-linked sideroblastic anemia and X-linked protoporphyria can result from one of more than 91 genetic mutations in the human erythroid-specific enzyme ALAS2. " 01/01/2019 - "One SNP (p.R559H) had markedly low purification yield indicating enzyme instability as the likely cause for XLSA in an elderly patient with x-linked sideroblastic anemia. " 12/01/2002 - "Mutations in the erythroid aminolevulinate synthase gene lead to a defective enzyme and are associated with the erythropoietic disorder X-linked sideroblastic anemia. " 01/01/2019 - "The most prevalent form of CSA is X-linked sideroblastic anemia, caused by mutations in the erythroid-specific δ-aminolevulinate synthase (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. " 01/01/2018 - "The most common form of CSA is X-linked sideroblastic anemia; it occurs because of mutations in the erythroid-specific δ-aminolevulinate synthase gene (ALAS2), which is the first enzyme of the heme biosynthesis pathway in erythroid cells. "
6.	Aminolevulinic Acid (Levulan)FDA Link 01/01/2022 - "X-linked sideroblastic anemia (XLSA) is associated with mutations in the erythroid-specific δ-aminolevulinic acid synthase (ALAS2) gene. " 01/01/2015 - "δ-aminolevulinic acid synthase 2 (ALAS2 ) polymorphism is used as a marker for X-linked sideroblastic anemia. " 08/17/2012 - "Mutations in the erythroid-specific aminolevulinic acid synthase gene (ALAS2) cause X-linked sideroblastic anemia (XLSA) by reducing mitochondrial enzymatic activity. " 08/01/1999 - "Recently, X-linked sideroblastic anemia has been shown to be caused by missense mutations in the delta-aminolevulinic acid synthase (ALAS) gene. " 02/16/2009 - "Recent kinetic and crystallographic data have facilitated an unprecedented understanding of how this important enzyme produces 5-aminolevulinate, and suggest possible directions for future research that may lead to treatments not only for X-linked sideroblastic anemia, but also other diseases."
7.	Proteins (Proteins, Gene)FDA Link 10/13/2016 - "A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia." 03/01/2005 - "For instance, the disease X-linked sideroblastic anemia with ataxia (XLSA/A) is due to a mutation in the ATP-binding cassette protein B7 (ABCB7) transporter that is thought to transfer [Fe-S] clusters from the mitochondrion to the cytoplasm. " 01/01/2003 - "Mutations in two such proteins, frataxin and ABCB7, cause Friedreich ataxia and X-linked sideroblastic anemia with ataxia, respectively, rendering other participants in this pathway functional candidates for hereditary ataxia syndromes. " 04/15/2003 - "A mitochondrial half-type ATP-binding cassette (ABC) protein, ABC7, plays a role in iron homeostasis in mitochondria, and defects in human ABC7 were shown to be responsible for the inherited disease X-linked sideroblastic anemia/ataxia. "
8.	AcidsIBA 04/11/2003 - "A three-dimensional structure model of 5-aminolevulinic acid synthase from human erythrocytes (ALAS 2) has also been constructed and used to map a range of naturally occurring human mutants that give rise to X-linked sideroblastic anemia. " 12/01/2002 - "X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. " 12/15/2000 - "X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. " 03/02/2023 - "We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta (SPTB) and 5-aminolevulinic acid synthase (ALAS2) genes. "
9.	ATP-Binding Cassette Transporters (ABC Transporters)IBA 01/01/1998 - "Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia." 04/15/2007 - "X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare syndromic form of inherited sideroblastic anemia associated with spinocerebellar ataxia, and is due to mutations in the mitochondrial ATP-binding cassette transporter Abcb7. " 01/01/2019 - "Loss-of-function mutations in the ATP-binding cassette (ABC) transporter of the inner mitochondrial membrane, ABCB7, cause X-linked sideroblastic anemia with ataxia, a phenotype that remains largely unexplained by the proposed role of ABCB7 in exporting a special sulfur species for use in cytosolic iron-sulfur (Fe-S) cluster biogenesis. "
10.	Adenosine Triphosphate (ATP)IBA 03/01/2005 - "For instance, the disease X-linked sideroblastic anemia with ataxia (XLSA/A) is due to a mutation in the ATP-binding cassette protein B7 (ABCB7) transporter that is thought to transfer [Fe-S] clusters from the mitochondrion to the cytoplasm. " 04/15/2003 - "A mitochondrial half-type ATP-binding cassette (ABC) protein, ABC7, plays a role in iron homeostasis in mitochondria, and defects in human ABC7 were shown to be responsible for the inherited disease X-linked sideroblastic anemia/ataxia. " 01/01/2019 - "Loss-of-function mutations in the ATP-binding cassette (ABC) transporter of the inner mitochondrial membrane, ABCB7, cause X-linked sideroblastic anemia with ataxia, a phenotype that remains largely unexplained by the proposed role of ABCB7 in exporting a special sulfur species for use in cytosolic iron-sulfur (Fe-S) cluster biogenesis. "

Therapies and Procedures

1.	Blood Transfusion (Blood Transfusions) 06/01/2001 - "Three children with congenital sideroblastic anaemia (SA) who were blood transfusion dependent underwent stem cell transplantation (SCT) from matched sibling donors. " 06/01/2001 - "Therapy for patients with congenital sideroblastic anaemia has been limited to blood transfusions and chelation. " 08/01/1983 - "The relationship between body iron status, degree of anaemia, erythroid expansion, age and sex has been studied in eight patients with congenital dyserythropoietic anaemia (CDA) and two patients with congenital sideroblastic anaemia, who had received no or very few blood transfusions and no medicinal iron during the course of their illness. " 05/07/1977 - "The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. " 12/11/1976 - "The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. "
2.	Subcutaneous Infusions 05/07/1977 - "The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. " 12/11/1976 - "The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. "
3.	Stem Cell Transplantation 06/01/2001 - "Congenital sideroblastic anaemia successfully treated using allogeneic stem cell transplantation." 06/01/2001 - "Three children with congenital sideroblastic anaemia (SA) who were blood transfusion dependent underwent stem cell transplantation (SCT) from matched sibling donors. "
4.	Therapeutics 06/01/2001 - "Therapy for patients with congenital sideroblastic anaemia has been limited to blood transfusions and chelation. "
5.	Intramuscular Injections 12/11/1976 - "The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. "