Diagnosis of Fanconi Anemia By Chromosome Breakage Tests Using 3 Different Scoring Systems and Whole Genome Sequencing Among Patients with Aplastic Anemia in Korean

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4792-4792
Author(s):  
Si Nae Park ◽  
Nam Hee Kim ◽  
Kyongok Im ◽  
Jee Soo Lee ◽  
Sungbin Choi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Scoring Systems ◽  
Chromosome Breakage ◽  
Whole Genome ◽  
Bone Marrow Failure Syndrome

Abstract BACKGROUD: Fanconi anemia (FA), an inherited bone marrow failure syndrome with impaired DNA repair system, is characterized by cytopenias, congenital abnormalities, and predisposition to malignancy as a consequence of chromosomal instability and hypersensitivity to DNA interstrand cross-linking agents. Differential diagnosis of FA and aplastic anemia requires integrated work-up including physical findings, bone marrow histologic findings and chromosome breakage test. Yet, there have been no consensus criteria for chromosome breakage test, which depend on each laboratory's own decision. The aim of our study was 1) to investigate the incidence of FA showing positive results for chromosome breakage test among patients diagnosed with aplastic anemia, and 2) to investigate the frequency of the gene mutations related to inherited bone marrow failure syndrome in patients with aplastic anemia. In addition to chromosome breakage test, we performed whole genome sequencing with bone marrow mononuclear cells in 18 pediatric patients with aplastic anemia whose bone marrow specimen was available. METHOD: We reviewed total 79 chromosome breakage tests from 67 patients who had been on suspicion of aplastic anemia between May 2005 and April 2015. MMC and DEB stress test were performed at concentration of 50ng/mL and 100ng/mL both on peripheral blood of suspicious patients and normal controls, respectively. The scoring of chromosome breakages test was performed, based on widely used 3 different scoring systems: those proposed by Jean Soulier, Barch MJ, and Arleen D. Auerbach. In each cases, we applied 3 different scoring systems and compared the concordance rate. In 16 among 67 patients, we performed whole genome sequencing. RESULTS: The median age of the pediatric patients was 11years (range, 7months - 19 years) and the male-to-female ratio was 1.39:1. Of 67 enrolled patients, 8 had been tested twice or 3 times because of ambiguous results. In these cases, we chose the last results. Five of 67 patients satisfied the all three criteria mentioned above, which shows 7.5% (5/67) of positive rates. Other 3 of 67 patients met only one or more of Soulier's prerequisites. Among those, one fulfilled both Barch MJ's system and Aeurbach's, and remain 2 patients were positive in each system, respectively. Mutation variants of BMF syndrome related genes were detected in 25% (4/16 patients); RPS19 (1 patient), PAX5 (1 patient), and FANC (3 patient). Inherited predisposition to myeloid leukemia related genes were detected in 56.3% (9/16 patients) and gene variants were MSH6 (5 patients), ATM (2 patients), PMS2 (1 patients), and MLH1 (1 patients). Coexisting somatic mutations of oncogene (ERB2) was detected in 6.3% (1/16 patients). Among 3 patients with fanconi anemia gene mutations, 2 patients showed positive results for chromosome breakage test and the other1patient showed negative results for chromosome breakage test. CONCLUSION: The frequency of FA based on chromosome breakage test among patients with pancytopenia suspicious of aplastic anemia was 7.5% by Soulier's prerequisites, but 9.0% when based on either of 3 different criteria. Molecular testing can additionally detect FA in 4 (25.0%) among 16 patients showing negative result by chromosome breakage test. Our study shows it is necessary to standardize a diagnostic scoring system as well as to develop complementary molecular test for accurate diagnosis of FA. Disclosures No relevant conflicts of interest to declare.

Unexpected Fanconi Anemia Diagnosis in Patients with Bone Marrow Failure.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1056-1056
Author(s):  
Fernando O. Pinto ◽  
Thierry Leblanc ◽  
Gwenaelle Le Roux ◽  
Helene Dastot ◽  
Moema Santos ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Clinical Features ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Somatic Mosaicism ◽  
Chromosome Breakage ◽  
Large Set ◽  
Chromosomal Breakage ◽  
Group A

Abstract Early diagnosis of Fanconi Anemia (FA) in patients with bone marrow failure is critical for optimal clinical management. However, the remarkably high clinical variability and the potential emergence of revertant hematopoietic cells (somatic mosaicism) can obscure and delay the diagnosis of FA. Here we addressed FA diagnosis in a prospective series of adult and pediatric patients who presented with bone marrow failure without clear overall clinical picture of FA. Sixty-six patients were classified into three groups: (1) bone marrow failure likely to be congenital, based on dysmorphic features or a family history [n=18], (2) aplastic anemia likely to be idiopathic [n=32], (3) patients with intermediate clinical features not classified into the former groups [n=16]. Of note, FA patients with typical clinical features were not included in the present study. FA diagnosis was evaluated using chromosome breakage test and FANCD2 immunoblot in PHA-stimulated-PBL. In addition, skin primary fibroblasts were analysed in order to overcome potential hematopoietic FA reversion. For that purpose, and considering that chromosome breakage tests are barely efficient in fibroblasts, we used FANCD2 immunoblot and also developped a new flow cytometry test based on MMC-sensitivity in fibroblasts (to detect downstream FA/BRCA groups). Using these approaches, we detected FA in 4 previously undiagnosed patients: a 35-years old patient from the congenital-like group; a 10-years old patient presenting as an idiopathic aplastic anemia without any FA signs; and two patients from the intermediate group: a 10-years old patient with an isolated thrombocytopenia, and a 50-years old patient presenting with pancytopenia/MDS and complete hematopoietic reversion. Importantly, FA diagnosis was definitely excluded in all other patients. In conclusion, we could identify a few unexpected FA cases in a series of patients with bone marrow failure. Therefore, the comprehensive use of a large set of tests is useful for accurate FA diagnosis. Classical chromosomal breakage tests in PBL appeared to be sufficient to exclude FA in idiopathic aplastic anemia, whereas fibroblast analysis can be necessary to definitely diagnose or exclude FA in other patients.

Hepatitis-associated Aplastic Anemia Presenting as a Familial Bone Marrow Failure Syndrome

2009 ◽  
Vol 31 (11) ◽  
pp. 884-887 ◽  
Author(s):  
Vicky Rowena Breakey ◽  
Stephen Meyn ◽  
Vicky Ng ◽  
Christopher Allen ◽  
Inderjeet Dokal ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Bone Marrow Failure Syndrome

scholarly journals Aplastic anemia: immunosuppressive therapy in 2010

2011 ◽  
Vol 3 (2s) ◽  
pp. 7 ◽  
Author(s):  
Antonio M. Risitano ◽  
Fabiana Perna
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
State Of The Art ◽  
Bone Marrow Failure ◽  
Standards Of Care ◽  
Bone Marrow Failure Syndrome ◽  
Clinical Observations ◽  
Immune Mediated ◽  
Experimental Works ◽  
Current Standards

Acquired aplastic anemia (AA) is the typical bone marrow failure syndrome characterized by an empty bone marrow; an immune-mediated pathophysiology has been demonstrated by experimental works as well as by clinical observations. Immunusuppressive therapy (IST) is a key treatment strategy for aplastic anemia; since 20 years the standard IST for AA patients has been anti-thymocyte globuline (ATG) plus cyclosporine A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. Here we review the state of the art of IST for AA in 2010, focusing on possible strategies to improve current treatments. We also discuss very recent data which question the equality of different ATG preparations, leading to a possible reconsideration of the current standards of care for AA patients.

Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3584-3586 ◽  
Author(s):  
Jaroslaw P. Maciejewski ◽  
Elaine M. Sloand ◽  
Olga Nunez ◽  
Carol Boss ◽  
Neal S. Young
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Aplastic Anemia ◽  
Neutrophil Count ◽  
Bone Marrow Failure ◽  
Interleukin 2 ◽  
Immunosuppressive Agent ◽  
Solid Organ ◽  
Bone Marrow Failure Syndrome ◽  
Humanized Monoclonal Antibody

AbstractIn contrast to severe aplastic anemia (sAA), the appropriate management of patients with moderate pancytopenia is unclear. In this study, we examined the efficacy of a humanized monoclonal antibody recognizing interleukin-2 receptor (daclizumab), which has proven to be a successful immunosuppressive agent in solid organ and bone marrow transplantation. We treated 17 patients with moderate aplastic anemia (mAA) with 1 mg/kg every 2 weeks for 3 months. mAA was defined as depression of 2 of the 3 blood counts: absolute neutrophil count 1200/mm3 or less, platelet count 70 000/mm3 or less, hemoglobin level 8.5 g/dL or lower, and absolute reticulocyte count 60 000/mm3 or less. The primary end point of our protocol was a hematologic response in at least one affected peripheral blood value. Daclizumab had little toxicity. Six of the 16 (38%) evaluable patients responded to treatment. Two patients with previously chronic disease showed complete return of normal counts, which were sustained for more than 2 years following treatment. Four patients had single-lineage responses. Two previously transfusion-dependent patients became transfusion independent; one patient with many neutropenia-related infections had a normal neutrophil count following treatment. Daclizumab appears safe; its efficacy in this pilot protocol suggests that expanded study of this monoclonal antibody in immune-mediated bone marrow failure syndrome is warranted. (Blood. 2003; 102:3584-3586)

scholarly journals Characterization of Pathogenic Variants and Clinical Phenotypes in 117 Japanese Fanconi Anemia Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3860-3860
Author(s):  
Minako Mori ◽  
Asuka Hira ◽  
Kenichi Yoshida ◽  
Hideki Muramatsu ◽  
Yusuke Okuno ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Exome Sequencing ◽  
Molecular Diagnosis ◽  
Fanconi Anemia ◽  
Direct Sequencing ◽  
Bone Marrow Failure ◽  
Whole Genome ◽  
Aberrant Splicing ◽  
Large Deletions ◽  
Complementation Groups

Abstract Objective: Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome associated with multiple congenital abnormalities and predisposition to malignancies, resulting from mutations in one of the 22 known FA genes (FANCA to W). The proteins encoded by these genes participate in DNA repair pathway (the FA pathway) for endogenous aldehyde damage. Compared to the situation in the US or Europe, the number of Japanese FA patients with genetic diagnosis was relatively limited. In this study, we reveal the genetic subtyping and the characteristics of mutated FA genes in Japanese population and clarify the genotype-phenotype correlations. Results: We studied 117 Japanese FA patients from 103 families (1996 to 2018). The diagnosis of FA was confirmed on the basis of chromosomal breakage tests and clinical features. Molecular diagnosis was obtained in 107 (91.5%) of the 117 patients through direct sequencing of FANCA and FANCG, MLPA analysis for FANCA, targeted exome sequencing (targeted-seq), and whole exome sequencing (WES) analysis (Figure 1). To provide genetic subtyping for the 10 unclassified cases, we tried to apply various technologies. Array CGH revealed large deletions in two FA-B and one FA-T cases. Whole genome sequencing and RNA-sequencing analysis identified splicing site or aberrant splicing mutations among three cases (one FA-B, one FA-C, and one FA-N). Collectively, 113 (97%) of Japanese 117 FA patients were successfully subtyped and a total of 219 mutated alleles were identified. FA-A and FA-G accounted for the disease in 58% and 25% of FA patients, respectively, whereas each of the other complementation groups accounted for less than 5% of FA cases. FANCB was the third most common complementation group (n=4) and only one FA-C case was identified in Japanese FA patients. In the 68 FA-A patients, we identified 130 mutant alleles that included 55 different FANCA variants (17 nucleotide substitutions, 16 small deletions/insertions, 12 large deletions, 1 large duplication and 9 splice site mutation). FANCA c.2546delC was the most prevalent (41/130 alleles; 32%). In the 29 FA-G patients, 57 mutant alleles were identified and seven different FANCG variants were detected. FANCG c.307+1G>C and 1066C>T accounted for most of FANCG mutant alleles (49/57; 88%) in the Japanese FA-G patients. The three hotspot mutations (FANCA c.2546delC, FANCG c.307+1G>C and c.1066C>T) existed at low prevalence (0.04-0.1%) in the whole-genome reference panel of 3554 Japanese individuals (3.5KJPN, Tohoku Megabank). Consistent with the paucity of the FA-C patients as opposed to the previous report (Blood 2000), the FANCC IVS4+4A mutation was absent in the 3.5KJPN database. We were able to examine the hematological outcomes in a subset of our cases (52 FA-A and 23 FA-G). Interestingly, the FA-G patients developed bone marrow failure (BMF) at a significantly younger age than FA-A patients (median age at onset of BMF: 3.1 years vs 5 years). Furthermore, the patients with the FANCA c.2546delC mutation had an increased risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), compared to FA-A patients without the mutation. In the rare complementation groups of FA, two FA-B cases with complete loss of FANCB gene and one FA-I patient with N-terminal premature termination codons revealed severe somatic abnormalities, consistent with VACTERL-H association. Two FANCD1 (BRCA2) patients and one FANCN (PALB2) patients did not experience bone marrow failure but developed early-onset malignancies (immature teratoma, T-lymphoblastic lymphoma, adenosquamous lung carcinoma, Wilms tumor). Conclusion: This is the largest series of subtyped Japanese FA patients to date and the results would be useful for future clinical management. To provide molecular diagnosis for FA in Japan, we suggest to start with PCR-direct sequencing of the three common mutations (FANCA c.2546delC, FANCG c.307+1G>C and FANCG c.1066C>T) along with MLPA assay for FANCA. These analyses would enable the identification of about 50% of the mutant alleles. For the rest of the cases, WES or targeted-seq analysis should be useful, however, large deletions and aberrant splicing need to be kept in mind. Disclosures Takaori-Kondo: Pfizer: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Janssen Pharmaceuticals: Honoraria.

scholarly journals Outcomes of Haploidentical Stem Cell Transplantation in Patients with Fanconi Anemia; A Systematic Review

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4308-4308
Author(s):  
Zunairah Shah ◽  
Israr Khan ◽  
Ali Shahbaz Baloch ◽  
Talha Awal ◽  
Sobia Aamir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bone Marrow ◽  
Fanconi Anemia ◽  
Research Funding ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Solid Organ ◽  
Bone Marrow Failure Syndrome ◽  
Post Transplant

Abstract Introduction Fanconi anemia (FA) is the most common inherited cause of bone marrow failure syndrome, with an incidence of approximately 1 out of 100,000 births per year and a prevalence of 1 in 360 000 live births. Clinical presentation is variable, ranging from classic Fanconi phenotype to absence of somatic abnormalities. Despite advances in understanding disease genetics and pathogenesis, hematopoietic stem cell transplant (HSCT) remains the only curative treatment option for FA patients. However, the future risk of solid organ malignancies persists post-transplant. Although outcomes of allogeneic HSCT for FA are improving steadily but remains suboptimal and often limited by donor availability- especially in countries lacking matched unrelated donor registry. For patients lacking a suitable donor, a trial of androgen is considered but is not curative, and around half of patients will not respond. Haploidentical HSCT has been successfully utilized in the management of acquired severe aplastic anemia and hematological malignancies but only limited published literature is available on its use in inherited bone marrow failure syndromes. We conducted this systematic review to explore survival outcomes of FA patients receiving haploidentical HSCT to assess feasibility of this treatment for patients lacking a matched donor. Methods We conducted a literature search on Pubmed, Cochrane, Google Scholar, open grey, and embase databases using the keywords; Haploidentical Transplant and Fanconi anemia. We screened 236 articles according to the Prisma diagram. After thoroughly reading the titles and abstracts, 13 articles were included for data extraction, and results were compiled. Results We analyzed thirteen studies with haploidentical transplant as a treatment for FA, 7 were retrospective, and 6 were prospective. Diagnosis of FA was established by chromosomal breakage analysis and genetic mutation testing. The preferred donor for a haploidentical transplant was a first-degree relative and mother/sibling in most cases. The total number of patients with FA and other disorder who received haploidentical transplants were n=340. The median age at HSCT was 6.7 (0.25-44) years. Two hundred six were male, and 134 were female. The most common conditioning regimen for FA patients was fludarabine, cyclophosphamide, and total body irradiation (TBI) followed by anti-thrombocyte globulin. Mehta. et al. evaluated haploidentical transplant without TBI in the conditioning regimen. The most common regimen to prevent graft versus host disease (GVHD) was cyclosporin and mycophenolate mofetil. Uppulur. R et al., Bonfim. C et al., Thakar. M.S et al. and Ayas, M et al. also used post-transplant cyclophosphamide for in vivo T cell depletion. Zubicaray. J et al and Strocchio. L et al. did not use any post-transplant therapy. Cumulative Overall survival reported was 79.1%. Cumulative acute GVHD was seen in 38.2%, while cumulative chronic GVHD was seen in 18.6% of patients. The most common adverse events were acute and chronic GVHD, Evans syndrome, steroid-induced osteoporosis, and diabetes. Respiratory syncytial virus, pneumonia, candida sepsis reactivation, hemorrhagic cystitis, and mucositis were the most common infections. Conclusion Fanconi anemia is an inherited bone marrow failure syndrome with somatic abnormalities and increased risk of hematological and solid organ malignancies. In FA, allogeneic hematopoietic cell transplantation (HCT) has been shown to restore normal hematopoiesis in patients with matched related donor HCT and has shown excellent long-term survival. Currently, limited data is available reporting outcomes of haploidentical HSCT for FA patients. More studies are required to establish safety and efficacy profiles. Figure 1 Figure 1. Disclosures Anwer: Allogene Therapeutics: Research Funding; GlaxoSmithKline: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding.

Mutations in the RNA Component of Telomerase, TERC, in Children with Aplastic Anemia and Myelodysplastic Syndrome: An NMDP Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3736-3736
Author(s):  
Joshua J. Field ◽  
Philip J. Mason ◽  
Yvonne J. Barnes ◽  
Allison A. King ◽  
Monica Bessler ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Aplastic Anemia ◽  
Stem Cell Transplant ◽  
Bone Marrow Failure ◽  
Juvenile Myelomonocytic Leukemia ◽  
Cell Transplant ◽  
Bone Marrow Failure Syndrome ◽  
Base Pair Deletion

Abstract Mutations in TERC, the RNA component of telomerase, result in autosomal dominant dyskeratosis congenita (DC), a rare bone marrow failure syndrome. DC is clinically heterogeneous and TERC mutations have been detected in a subset of patients previously diagnosed with idiopathic aplastic anemia (AA) and myelodysplastic syndrome (MDS). Unrecognized TERC mutations are clinically relevant as patients with DC respond poorly to immunotherapy and have an increased risk of complications following conventional conditioning for stem cell transplant (SCT). We aimed to determine the frequency of TERC mutations in pediatric patients with AA and MDS who require a SCT. We obtained 315 blood or bone marrow samples from the National Donor Marrow Program Registry from children under age 18 with bone marrow failure who underwent an unrelated stem cell transplant. We screened these samples for mutations in the TERC gene using direct DNA sequencing. To exclude polymorphisms, we also screened 537 racially diverse healthy controls. The study group was composed of patients with MDS (n=151), AA (n=123), and juvenile myelomonocytic leukemia (JMML) (n=41), which may be difficult to distinguish from MDS. The mean age at the time of transplant was 9 years. We found sequence alterations in the promoter region of TERC in 2 patients. A 2 base pair deletion (-240delCT) was identified in a 4 year-old child with MDS and a 1 year-old child with JMML was found to have a point mutation (-99C→G), which was identified previously in an 18 year-old patient with paroxysmal nocturnal hemoglobinuria and is known to affect the Sp1 binding site. The pathogenicity of this mutation is unclear. In summary, our findings suggest that screening for TERC gene mutations is unlikely to diagnose occult DC in children with severe bone marrow failure who require a stem cell transplant but have no clinical features or history to suggest a familial bone marrow failure syndrome.

Telomerase Gene Mutation Screening and Telomere Length Detection in Chinese Patients with Bone Marrow Failure Syndrome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1047-1047
Author(s):  
Bing Han ◽  
Bo Liu ◽  
Yongqiang Zhao
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Small Group ◽  
Telomere Length ◽  
Gene Mutation ◽  
Bone Marrow Failure ◽  
Chinese Patients ◽  
Chinese People ◽  
Bone Marrow Failure Syndrome ◽  
Tert Mutation

Abstract Background Acquired bone marrow failure syndrome (BMF) is a group of diseases include aplastic anemia(AA), melodysplastic syndrome (MDS) and paraoxymal nocturnal hemoglobinuria (PNH). Some BMF patients have short telomeres in their peripheral nucleated cells. The length of telomere is maintained by a group of enzymes called telomerase complex. The core components of this complex are a RNA template and a reverse transcriptase, called TERC and TERT, respectively. Recently several studies in the west and Japan have disclosed the presence of telomerase complex gene mutation in a small group of patients with acquired bone marrow failure. They speculated that this small group of patients might represent a subset of cryptogenic Dyskeratosis Congenita (DKC), in which the premature exhaustion of hematopoietic reservoir is caused by mutations in the telomerase gene. This group of patients, though very small in number, would benefit from early bone marrow transplantation instead of traditional immunosuppressive therapy. The incidence of aplastic anemia in Chinese people is relatively high compared with that in the western country. But there has so far been no study in China about the incidence of telomerase gene mutation in acquired bone marrow failure and its relationship with telomere length. Objectives To study the incidence of telomerase gene (namely TERC and TERT ) mutation in Chinese patients with acquired bone marrow failure and explore its relationship with telomere shortening. Methods Blood samples from 90 patients with AA, MDS, and PNH in northern China were collected and performed TERC and TERT mutation analysis. Telomere length was measured by Southern blotting and compared with their normal counterparts. Results 2 TERC mutations (n37 A→G, reported previously ; n66G→C) and 2 TERT mutations (n1870G→T (E/*); n1780G→T (S/I) ) were identified in 90 BMF patients. Among them, 3 mutations are reported first time. 1 patient with TERT mutation, however, was finally diagnosed as DKC instead of acquired AA, making the incidence of telomerase gene mutation in Chinese people with acquired bone marrow failure 3.4%, similar to that of the western people. Southern Blot analysis showed the small group of patients carrying TERC and TERT mutations has very short telomeres, compared with normal controls and with their aplastic counterparts. Conclusions The incidence of telomerase gene mutation in Chinese people with acquired bone marrow failure is 3.4%, similar to that of the western people. This small group of patients has very short telomeres, it is thus clinically important to screen for this small group of patients.

scholarly journals Clinical approach to marrow failure

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 329-337 ◽  
Author(s):  
Akiko Shimamura
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Medical Management ◽  
Bone Marrow Failure ◽  
Clinical History ◽  
Clinical Approach ◽  
Careful Attention ◽  
Bone Marrow Failure Syndrome ◽  
Bone Marrow Failure Syndromes ◽  
Molecular Pathophysiology

Abstract The treatment and medical management of aplastic anemia fundamentally differ between patients with inherited versus acquired marrow failure; however, the diagnosis of an inherited bone marrow failure syndrome is frequently obscure. Recent exciting advances in our understanding of the molecular pathophysiology of the inherited bone marrow failure syndromes have resulted in a profusion of new tests to aid in diagnosis. This in turn has raised questions regarding the appropriate choice of testing for the patient presenting with aplastic anemia. Important clues to the diagnosis of an inherited marrow failure syndrome may be gleaned from careful attention to the clinical history, physical exam, and laboratory workup.

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