Abstract：
BACKGROUND: XLSA may be confused clinically with MDS-RARS, which can have patient management implications.
BACKGROUND: Sideroblastic anemia is categorized as a rare type of anemia by National Organization for Rare Disorders. Fewer than 200 cases with less than 100 unrelated probands have been described for X-linked recessive sideroblastic anemia (XLSA). XLSA is the most common type of non-syndromic congenital sideroblastic anemias (CSA), with almost 40% of all CSA cases involving mutations in the ALAS2 (δ- aminolaevulinic acid synthase) gene. Male patients (two-thirds of known cases) usually present in childhood or adolescence with symptoms of anemia, while female patients present in middle age.
METHODS: We present a case of XLSA in a male patient with symptom-onset in middle age. He initially presented with symptoms of anemia and received multiple blood transfusions over a period of 10 years. Subsequent bone marrow biopsy showed a hypercellular bone marrow with erythroid hyperplasia, increased iron and ringed sideroblasts consistent with refractory anemia with ringed sideroblasts, no abnormal karyotype in cytogenetics, and normal flow cytometry results. A liver biopsy showed hemosiderotic changes, and he was initially considered to have myelodysplastic syndrome-refractory anemia with ringed sideroblasts (MDS-RARS). Genetic testing, including SF3B1 gene mutation, revealed no findings suggestive of MDS. The patient was then started on iron chelating agents and pyridoxine with improvement in anemia and did not require any further transfusions with significant improvement in his symptoms. A hereditary anemia NGS gene sequencing and deletion/duplication panel was then done which showed pathogenic X-linked recessive hemizygous mutation involving ALAS2 gene-OMIM 301300. Response to the pyridoxine treatment, absence of SF3B1 gene mutation, and presence of ALAS2 gene mutation helped confirm the diagnosis of XLSA in our patient.
CONCLUSIONS: This case report highlights the necessity for extensive workup in patients with sideroblastic anemia, given the rarity of XLSA and similarity in its clinical symptoms to MDS-RARS, and the need for its early diagnosis. In our patient, iron overload and subsequent liver cirrhosis developed due to multiple transfusions for refractory sideroblastic anemia which was treated as MDS-RARS and could have been avoided if XLSA had been suspected earlier in the course of the disease.
BACKGROUND: Sideroblastic anemia is categorized as a rare type of anemia by National Organization for Rare Disorders. Fewer than 200 cases with less than 100 unrelated probands have been described for X-linked recessive sideroblastic anemia (XLSA). XLSA is the most common type of non-syndromic congenital sideroblastic anemias (CSA), with almost 40% of all CSA cases involving mutations in the ALAS2 (δ- aminolaevulinic acid synthase) gene. Male patients (two-thirds of known cases) usually present in childhood or adolescence with symptoms of anemia, while female patients present in middle age.
METHODS: We present a case of XLSA in a male patient with symptom-onset in middle age. He initially presented with symptoms of anemia and received multiple blood transfusions over a period of 10 years. Subsequent bone marrow biopsy showed a hypercellular bone marrow with erythroid hyperplasia, increased iron and ringed sideroblasts consistent with refractory anemia with ringed sideroblasts, no abnormal karyotype in cytogenetics, and normal flow cytometry results. A liver biopsy showed hemosiderotic changes, and he was initially considered to have myelodysplastic syndrome-refractory anemia with ringed sideroblasts (MDS-RARS). Genetic testing, including SF3B1 gene mutation, revealed no findings suggestive of MDS. The patient was then started on iron chelating agents and pyridoxine with improvement in anemia and did not require any further transfusions with significant improvement in his symptoms. A hereditary anemia NGS gene sequencing and deletion/duplication panel was then done which showed pathogenic X-linked recessive hemizygous mutation involving ALAS2 gene-OMIM 301300. Response to the pyridoxine treatment, absence of SF3B1 gene mutation, and presence of ALAS2 gene mutation helped confirm the diagnosis of XLSA in our patient.
CONCLUSIONS: This case report highlights the necessity for extensive workup in patients with sideroblastic anemia, given the rarity of XLSA and similarity in its clinical symptoms to MDS-RARS, and the need for its early diagnosis. In our patient, iron overload and subsequent liver cirrhosis developed due to multiple transfusions for refractory sideroblastic anemia which was treated as MDS-RARS and could have been avoided if XLSA had been suspected earlier in the course of the disease.
摘要：
背景：XLSA在临床上可能与MDS-RARS混淆，这可能会对患者管理产生影响。
背景：全国罕见疾病组织将铁粒幼细胞性贫血归类为一种罕见类型的贫血。描述了X连锁隐性铁粒母细胞性贫血（XLSA）的病例少于200例，其中无关先证者少于100例。XLSA是最常见的非综合征性先天性铁粒母细胞贫血（CSA），所有CSA病例中几乎40％涉及ALAS2（δ-氨基乙酰丙酸合酶）基因突变。男性患者（已知病例的三分之二）通常在儿童或青春期出现贫血症状，而女性患者出现在中年。
方法：我们介绍了一例中年时出现症状的男性患者的XLSA。他最初出现贫血症状，并在10年的时间内接受了多次输血。随后的骨髓活检显示骨髓高细胞伴红系增生，增加的铁和环状侧生细胞与难治性贫血与环状侧生细胞一致，细胞遗传学中没有异常核型,和正常的流式细胞术结果。肝活检显示含铁血黄素的改变,他最初被认为患有骨髓增生异常综合征-难治性贫血，伴有环状铁皮母细胞（MDS-RARS）。基因检测,包括SF3B1基因突变，没有发现提示MDS。然后患者开始服用铁螯合剂和吡哆醇，贫血得到改善，并且不需要任何进一步的输血，其症状得到显着改善。然后进行遗传性贫血NGS基因测序和缺失/重复小组，显示涉及ALAS2基因-OMIM301300的致病性X连锁隐性半合子突变。对吡哆醇治疗的反应，无SF3B1基因突变，ALAS2基因突变的存在有助于证实我们患者的XLSA诊断。
结论：本病例报告强调了对铁粒幼细胞性贫血患者进行广泛检查的必要性，考虑到XLSA的罕见性以及其临床症状与MDS-RARS的相似性，以及早期诊断的必要性。在我们的病人身上，铁超负荷和随后的肝硬化是由于多次输血治疗难治性铁粒幼细胞性贫血而发展的，这种贫血被视为MDS-RARS，如果在病程早期怀疑XLSA，则可以避免。
背景：全国罕见疾病组织将铁粒幼细胞性贫血归类为一种罕见类型的贫血。描述了X连锁隐性铁粒母细胞性贫血（XLSA）的病例少于200例，其中无关先证者少于100例。XLSA是最常见的非综合征性先天性铁粒母细胞贫血（CSA），所有CSA病例中几乎40％涉及ALAS2（δ-氨基乙酰丙酸合酶）基因突变。男性患者（已知病例的三分之二）通常在儿童或青春期出现贫血症状，而女性患者出现在中年。
方法：我们介绍了一例中年时出现症状的男性患者的XLSA。他最初出现贫血症状，并在10年的时间内接受了多次输血。随后的骨髓活检显示骨髓高细胞伴红系增生，增加的铁和环状侧生细胞与难治性贫血与环状侧生细胞一致，细胞遗传学中没有异常核型,和正常的流式细胞术结果。肝活检显示含铁血黄素的改变,他最初被认为患有骨髓增生异常综合征-难治性贫血，伴有环状铁皮母细胞（MDS-RARS）。基因检测,包括SF3B1基因突变，没有发现提示MDS。然后患者开始服用铁螯合剂和吡哆醇，贫血得到改善，并且不需要任何进一步的输血，其症状得到显着改善。然后进行遗传性贫血NGS基因测序和缺失/重复小组，显示涉及ALAS2基因-OMIM301300的致病性X连锁隐性半合子突变。对吡哆醇治疗的反应，无SF3B1基因突变，ALAS2基因突变的存在有助于证实我们患者的XLSA诊断。
结论：本病例报告强调了对铁粒幼细胞性贫血患者进行广泛检查的必要性，考虑到XLSA的罕见性以及其临床症状与MDS-RARS的相似性，以及早期诊断的必要性。在我们的病人身上，铁超负荷和随后的肝硬化是由于多次输血治疗难治性铁粒幼细胞性贫血而发展的，这种贫血被视为MDS-RARS，如果在病程早期怀疑XLSA，则可以避免。
