Pearson syndrome in a Diamond-Blackfan anemia cohort

Alter, Blanche P.

doi:10.1182/blood-2014-04-571687

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…Inherited and acquired conditions should be always considered in the differential diagnosis, in particular Schwachman-Diamond syndrome, Diamond-Blackfan anemia, and congenital sideroblastic anemias. 18,19 Our review confirms that a BMA performed in the first month of life can be less informative than a BMA performed later. In the first month of life, 16.7% of patients with PS had no typical BM features (Figure 2).…”

Section: Discussionsupporting

confidence: 62%

“…The diagnosis of PS in newborns is often difficult, because its clinical features may overlap with those of other more common conditions (infectious, neuromuscular, hematological, metabolic, or digestive diseases), and BM features suggestive of PS may be entirely or partially lacking. Inherited and acquired conditions should be always considered in the differential diagnosis, in particular Schwachman–Diamond syndrome, Diamond–Blackfan anemia, and congenital sideroblastic anemias …”

Section: Discussionmentioning

confidence: 99%

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Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature

Tadiotto

Maines²,

Degani

et al. 2017

Pediatric Blood & Cancer

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Pearson syndrome (PS) is a rare mitochondrial disorder that usually presents with transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction, and lactic acidosis. Typical bone marrow (BM) features are vacuolization in hematopoietic progenitors, hypocellularity, and ringed sideroblasts. At the neonatal age, PS may have a variable clinical onset. Moreover, there is little information about BM features at this age and the timing of their presentation. We report a neonatal case of PS that presented with refractory anemia and atypical BM features. We reviewed the BM findings in neonatal-onset PS cases to stress the importance and limitations of BM evaluation at this age.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature

Tadiotto

Maines²,

Degani

et al. 2017

Pediatric Blood & Cancer

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“…We conservatively identified 30 (6%) rare and predicted damaging genotypes in known or suspected red cell disorder genes that were non-RP genes ( Table 3). Although the majority of these were in CECR1 (9) or were mitochondrial deletions indicative of Pearson's Syndrome (7), as has been previously reported 71 , we identified several genes of interest that were mutated in a small number of cases. First, our cohort contained five individuals with We observed an exome-wide significant association between rare LoF dominant mutations in RPS19, RPL5, RPS26, RPL11, and RPS10, 5 of the most commonly mutated DBA genes.…”

Section: Phenocopies Misdiagnoses and Non-rp Gene Mutationsmentioning

confidence: 60%

The Genetic Landscape of Diamond-Blackfan Anemia

Ulirsch

Verboon

Kazerounian

et al. 2018

Preprint

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Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 1 in 100,000 to 200,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this genetically heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). Overall, we identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported genes encoding for a diverse set of ribosomal proteins (RPs). Using WES exon coverage estimates, we were able to identify and validate 31 deletions in DBA associated genes. We also observed an enrichment for extended splice site mutations and validated the diverse effects of these mutations using RNA sequencing in patientderived cell lines. Leveraging the size of our cohort, we observed several robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. In addition to comprehensively identifying mutations in known genes, we further identified rare mutations in 7 previously unreported RP genes that may cause DBA. We also identified several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this comprehensive report should not only inform clinical practice for DBA patients, but also the design and analysis of future rare variant studies for heterogeneous Mendelian disorders.

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“…En una revisión de una cohorte de 362 pacientes con diagnóstico establecido de anemia de Blackfan-Diamond en los que se pretendía encontrar posibles pacientes afectos de síndrome de Pearson que hubieran sido diagnosticados erróneamente, 8 de ellos (2,2%) fueron, finalmente, diagnosticados con este síndrome. 11 También debe tenerse en cuenta, en el diagnóstico diferencial, el síndrome de Shwachman-Diamond, que presenta insuficiencia pancreática exocrina y disfunción de médula ósea. 12 El diagnóstico de certeza se realiza mediante el estudio genético del ADN mitocondrial con Southern blot y amplificación completa de ADN mitocondrial mediante PCR-largo.…”

Section: Discussionunclassified

Anemia arregenerativa en el lactante: 2 casos de síndrome de Pearson

et al. 2017

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Presentación de casos clínicos RESUMEN La anemia es frecuente en lactantes, y, aunque su causa, habitualmente, es banal, debe establecerse un diagnóstico etiológico adecuado. Cuando la anemia es arregenerativa, puede deberse a aplasia medular, síndrome mielodisplásico, infiltración medular o déficits de factores hematopoyéticos. Otra posible causa es el síndrome de Pearson, una rara enfermedad mitocondrial que se presenta con anemia asociada a otras citopenias, insuficiencia pancreática, acidosis láctica y gran variabilidad en su presentación clínica condicionada por la heteroplasmia. Es característico encontrar en el aspirado/biopsia de médula ósea vacuolización de los precursores de serie roja y sideroblastos en anillo. El diagnóstico de certeza se establece mediante el estudio genético del ácido desoxirribonucleico mitocondrial con Southern blot (amplificación completa de ácido desoxirribonucleico mitocondrial mediante reacción en cadena de la polimerasa-largo), que obtiene deleción del 70%-80% de 4977 pb (DNAm 8343-13459). No existe tratamiento curativo y las medidas son de soporte. Es frecuente el fallecimiento en los primeros años de vida. Se presentan dos casos de lactantes con síndrome de Pearson.

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Pearson syndrome in a Diamond-Blackfan anemia cohort

Cited by 7 publications

References 6 publications

Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature

Bone marrow features in Pearson syndrome with neonatal onset: A case report and review of the literature

The Genetic Landscape of Diamond-Blackfan Anemia

Anemia arregenerativa en el lactante: 2 casos de síndrome de Pearson

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