Cases Of Sideroblastic Anemia Research Articles

Two cases of sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome in Chinese Han children caused by novel compound heterozygous variants of the TRNT1 gene

Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) syndrome is a serious autosomal recessive genetic disease. So far, <40 cases have been reported worldwide, and only one case has been reported in China. The main clinical features of SIFD are sideroblastic or microcytic anemia, immune deficiency, and recurrent episodes of inflammation. Here, we describe two unrelated cases of SIFD from China with different clinical manifestations and mild symptoms. Patient 1 was hospitalized at the age of 3.5 years due to persistent joint swelling with imaging of multiple joint effusions. Patient 2 was hospitalized at the age of 12 years due to repeated rashes on both lower limbs and oral ulcers. SIFD was detected using gene testing, which revealed the following compound heterozygous variants in TRNT1 in cases 1 and 2, respectively: c.88A > G/c.363G > T and c.302 T > C/c.1234cC > T. Searches of the HGMD databases revealed that these variants were all novel. Molecular dynamics simulations revealed that the missense variants c.363G > T and c.302 T > C would cause changes in protein structure and thus affect protein function. Finally, through literature reviewing, we found that the mortality in cases of SIFD was approximately 44% (14/32), and about 79% of individuals who died carried the hot-spot mutation c.668 T > C. Moreover, variants in the non-coding region were significantly more common among patients who died than among survivors. Our cases further expand the existing knowledge of the phenotype and variation spectrums of SIFD and suggest that genomic diagnosis is valuable for the hierarchical clinical management of this disease.

Somatic Mutations in Splicing Factor 3b, Subunit 1 (SF3B1) Are a Useful Biomarker to Differentiate Between Clonal and Non-Clonal Causes of Sideroblastic Anemia

Background: Sideroblastic anemia (SA) can present as congenital SA (CSA), acquired clonal SA, and acquired reversible SA. Patients (pts) with SA have anemia and ring sideroblasts (RS). Acquired clonal SA is often linked to myelodysplastic syndromes (MDS) or myelodysplastic/ myeloproliferative neoplasms (MDS/MPN). Clinico-pathologic overlap features, unmet morphologic and/or cytogenetic criteria complicate the diagnosis of SA leading to delayed therapies. Currently the diagnosis of SA is based on bone marrow (BM) examination and routine blood tests. There is a need to find easily testable biomarkers that can lead to faster diagnosis of clonal and non-clonal SA. Somatic mutation in splicing factor 3b, subunit 1 (SF3B1) are frequent in MDS-RS and MDS/MPN-RS and have been closely associated with RS.Objective:SF3B1 mutations can be a useful diagnostic biomarker for pts with acquired clonal SA who present with cytopenias and/or minimal morphologic changes suspicious of MDS and MDS/MPN but not sufficient to make a definitive diagnosis.Patients and Methods: Six pts with SA at presentation and seen at Cleveland Clinic were included in this study. The median age was 38 years (range, 6-75). Blood tests and BM biopsy showed persistent anemia [Hgb, 10.5 g/dL (range, 8.8-13)], RS [numerous (3 pts), 15% (1 pt), rare (1 pt) and >15% (2 pts)], 3/6 pts had minimal erythrodysplasia with 1 pt having a mild megakaryocytic dysplasia, 3 pts had hypercellular (60-90%), 2 pts had normocellular (50%, 80%) and 1 pt had hypocellular BM (30%) for age, and < 5% BM (2%=2 pts; 1%=1 pt; 3%=1 pt). Two pts had PLT count > 400 k/uL, 3 pts had > 100 k/uL, and 1pt <100 k/uL. Leukocytosis was observed in 2, leukopenia in 1, and neutropenia in 2 pts. Iron studies were unremarkable Molecular analysis was performed on SF3B1 (all exons), PRPF8 (exons 15, 25, 33), U2AF1 (exons 1, 6, 7), SRSF2 (exons 1, 2), DNMT3A (18-23), EZH2 (exons 18, 19) and IDH1/2 (exon 4). BCR/ABL p210 transcripts were assessed by RT-PCR. JAK2 (exon 14) was assessed by melting curve analysis.Results: All pts presented with sustained anemia, RS w/o or with minimal BM dysplasia, and normal karyotype. SF3B1 mutations (K666N and K700E) were detected in 2 pts (pts#2 and 6) before the clonal disease manifested. The first pt was a 75-year-old man with leukocytosis, transfusion-independent anemia, and fatigue. At the time of SF3B1 molecular testing the BM was hypercellular (60%) with <10%, megakaryocytic dysplasia, 2% blasts and 15% RS. JAK2 and BCR-ABL were wild type (WT). Later on, the patient developed hepatomegaly, his cytopenias worsened requiring RBC transfusions, and a repeat BM biopsy showed more prominent dysplasia of erythroid cells and megakaryocytes. The second pt was a 51-year-old man with fatigue, low WBC= 3.0 k/uL, ANC=0.7 k/uL, and PLTs=113 k/uL and macrocytic anemia (MCV=106 fL and Hgb=12.2 g/dL). His spleen was borderline enlarged (14 cm). BM biopsy showed 90% cellularity, erythroid hyperplasia, rare dyserythropoiesis and 60% RS. Suspicion for a possible MDS was raised although morphology was inconclusive. SF3B1 mutation (K700E) confirmed the clonality of the disease. A few months later, the pt developed worsening counts and overt MDS was confirmed by BM biopsy. All SF3B1WT pts were WT also for other genes known to be mutated in MDS and MDS/MPN like PRPF8, U2AF1, SRSF2, DNMT3A, IDH1/2, and EZH2. Only genetic tests showed an ALAS2 mutation in pt#1 and a paternally inherited duplication of 10q23.31 in pt#3. Both pts were diagnosed with CSA. Clinical history and work up assessed the same diagnosis for pt#4. Pt#5 presented with neutropenia and anemia. BM biopsy showed no dysplasia, 50% BM cellularity, trilineage maturation, and 25% RS. The presence of RS appeared to be induced by the use of an antibiotic prior the BM biopsy. Patient’s cytopenias and RS resolved after drug cessation.Conclusion: This case series although conducted in few pts provides important insights in the diagnostic use of molecular genetics in clinical practice. Often SA pts come to the clinic with inconclusive morphologic features of MDS or MDS/MPN. The presence of SF3B1 mutations may serve as an additional tool that can help differentiating between clonal and non-clonal cases of SA. In both pts, SF3B1 mutations anticipated the subsequent overt manifestation of clinical MDS or MDS/MPN phenotype. The collection of a larger cohort of pts is ongoing in order to further confirm this finding. DisclosuresNo relevant conflicts of interest to declare.

Sideroblastic anemia due to linezolid in a patient with a left ventricular assist device

An acquired form of sideroblastic anemia has been described in association with several drugs, especially anti-microbial agents. A case of sideroblastic anemia is presented in a patient with a left ventricular assist device drive-line infection who was receiving linezolid, an antibiotic used for serious infections with gram-positive organisms. This patient’s anemia resolved after discontinuation of the drug; he subsequently underwent an uncomplicated orthotopic heart transplant with no recurrence of anemia. As linezolid has been shown to have hematologic side effects, blood count monitoring is recommended in patients receiving this drug for long-term therapy.

Concise review: Genetic bases for sideroblastic anemia

The best-documented mode of transmission of familial sideroblastic anemia is as an X-linked trait. Mitochondrial mutation has also occasionally been noted in association with sideroblastic anemia, but it is likely to be present more often than has so far been described. It should especially be suspected in cases of inherited multisystem disease, where the pedigrees do not indicate a sex predominance among those affected, and where there is no evidence of transmission by the paternal line. Sporadic cases of sideroblastic anemia may represent mitochondrial mutations either at the germ cell or the somatic cell, and the most sensitive strategy of screening for both would be the study of mitochondrial DNA from circulating erythrocytes. It seems likely that such studies would extend the understanding of mitochondrial function and disease.

A Case of Sideroblastic Anemia with Chromosome Abnormality of Trisomy 8

A Case of Sideroblastic Anemia with Chromosome Abnormality of Trisomy 8

A Case of Sideroblastic Anemia with Chromosome Abnormality of Trisomy 8, Terminating in Acute Myelogenous Leukemia

A Case of Sideroblastic Anemia with Chromosome Abnormality of Trisomy 8, Terminating in Acute Myelogenous Leukemia

Sideroblastic Anemia Associated With Penicillamine Therapy

• A case of sideroblastic anemia followed the administration of D-penicillamine. Immediate correction of the abnormality in hemoglobin synthesis was noted following cessation of penicillamine therapy and institution of hydrochloride therapy. The patient's diet was not deficient in pyridoxine and no other causes of acquired sideroblastic anemia were present. It is of interest that abnormalities in pyridoxine metabolism have been reported in rats receiving L-penicillamine. (<i>Arch Intern Med</i>1981;141:1713-1714)

A Case of Sideroblastic Anemia with Dermal Photosensitivity and Increased Erythrocyte Protoporphyrin

A Case of Sideroblastic Anemia with Dermal Photosensitivity and Increased Erythrocyte Protoporphyrin

Bone marrow delta-aminolevulinic acid synthetase activity in hematological disorders.

An improved radiochemical method to measure the o-aminoJevulinic acid (ALA) synthetase activity in human bone marrow erythroblasts by incubating bone marrow cell homogenate with 14C-succinate and succinyl CoA generating system has been reported. Studies were made to ob­ tain the optimal conditions for the enzyme assay and to confirm the reliability of the assay pro­ cedures. ALA-synthetase in erythroblasts was found to be decreased in all 3 cases of iron deficiency anemia and 3 cases of l3-thalassemia minor. In 5 cases of idiopathic sideroblastic anemia, the enzyme activity was markedly decreased. A case of sideroblastic anemia, who restored normal erythropoiesis following the administration of pyridoxal phosphate (PLP) showed low PLP level in serum & blood as well as in vivo evidence of PLP deficiency and an in vitro stimulation of ALA­ synthetase activity by PLP. Erythroblasts of 4 patients with erythroleukemia showed diminished bone marrow ALA-synthetase activity.

Plasma Iron and Erythrocytic Glutathione Peroxidase Activity

The red cell glutathione-peroxidase (GSH-Px) activity of 9 normal subjects is compared with that of 15 cases of iron deficiency anaemia and with 13 cases of heterozygous beta-thalassemia with the same degree of anaemia and hypochromia. 2 cases of sideroblastic anaemia with high serum iron levels were also examined. Enzymatic activity was found to be significantly decreased in iron deficiency anaemia (about 55% of normal range), while it was not affected in heterozygous beta thalassaemia and it was increased in the 2 cases of sideroblastic anaemia. Moreover, GSH-Px activity exhibited a significant correlation with serum iron levels in all the patients studied. The observed modifications in GSH-Px activity are not correlated with erythrocyte ageing because reticulocyte-poor fractions exhibited GSH-Px activity which was not significantly reduced in respect of the reticulocyte-rich ones. These data seem to suggest that iron has a crucial connection with erythrocyte GSH-Px and that the enzyme deficiency may be of some importance in explaining the decreased red cell survival observed in severe iron-deficiency anaemias.

A case of primary acquired sideroblastic anemia with deficient -aminolevulinic acid synthetase activity in bone marrow erythroblasts.

A case of primary acquired sideroblastic anemia is described, in whom erythroblasts showed markedly reduced δ-aminolevulinic acid synthetase activity. The patient, 68-year-old Japanese female, was admitted with a history of anemia and congestive heart failure of 3 year duration. By hematological study, marked hypochromic anemia without apparent morphologic aberration was noted. Examination of bone marrow disclosed the intensive erythroid hyperplasia with minor megaloblastoid changes and maturation arrest. Iron stores in bone marrow were greatly increased with predominating sideroblasts. Serum iron was elevated and ferrokinetic study indicated normal rate of iron clearance and depressed red cell iron utilization. In the studies on porphyrin metabolism, incorporation of 14C-glycine into heme and activity of S-aminolevulinic acid (ALA) synthetase were found to be greatly reduced. Although there have been several reports on the defects in the heme synthetic pathway in sideroblastic anemia, this is a first case of sideroblastic anemia with deficient ALA synthetase activity demonstrated by a direct method.

Electron Microscopic Observation on a Case of Sideroblastic Anemia

Electron Microscopic Observation on a Case of Sideroblastic Anemia Get access Yukio SATOW, Yukio SATOW Search for other works by this author on: Oxford Academic PubMed Google Scholar Tsuneto IMAHASHI, Tsuneto IMAHASHI *Department of Genetic Pathology Reseurch Institute for Nuclear Medicine and Biology Hiroshima University HiroshimaJapan Search for other works by this author on: Oxford Academic PubMed Google Scholar Akio KAGIMOTO Akio KAGIMOTO **Department of Inteynal MedicineJapan Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Electron Microscopy, Volume 16, Issue 3, 1967, Pages 283–284, https://doi.org/10.1093/oxfordjournals.jmicro.a049569 Published: 01 January 1967 Article history Received: 24 December 1966 Published: 01 January 1967

HEREDITARY SIDEROBLASTIC ANAEMIA.

Cases of sideroblastic anaemia without an obvious underlying cause and with other members of the family affected by what is clearly the same condition are few in the literature, and in most reports the family study has not been sufficiently extensive to establish the type of inheritance or even to ensure that the cause is hereditary rather than environmental.