Diamond Blackfan Anemia: A Nonclassical Patient With Diagnosis Assisted by Genomic Analysis

Abstract

Summary Diamond Blackfan anemia (DBA) is an inherited syndrome usually presenting with severe macrocytic anemia in infancy, paucity of erythroid precursors in the bone marrow, and congenital anomalies. We describe a child with mild, transfusion independent normocytic anemia whose diagnosis of DBA was established by identification of a novel de novo mutation disrupting normal splicing of the ribosomal protein RPL5. The diagnosis of DBA was confirmed by elevated erythrocyte adenosine deaminase levels and an abnormal ribosomal RNA profile. This case demonstrates the usefulness of genomic analysis in establishing the diagnosis of DBA in patients with a nonclassical presentation of the disease.

Diamond–Blackfan anemia with mutation in RPS19: A case report and an overview of published pieces of literature

“…[ 22 ] There are mounting pieces of evidence of diagnosing of the nonclassical presentation of DBA and generates more apprehension. [ 4 82 , 83 ] In the current case, the focal evidence for the determination of DBA was the persistent isolated anemia, and normal marrow cellularity with markedly depressed erythropoiesis was in the same as mentioned earlier study report. [ 84 ] DBA patients with late-onset anemia or a relatively mild course have been reported.…”

“…[ 84 ] DBA patients with late-onset anemia or a relatively mild course have been reported. [ 82 85 ] Multiple previous studies showed that a meager number of patients were identified as DBA cases after 12 months of age, with insignificant anemia requiring treatment or intervention at all. [ 6 13 , 86 87 88 89 ] The present case, along with those previously reported, highlights the phenotypic heterogeneity of DBA and the prerequisite to contemplate this illness even in patients with no evident congenital glitches and only a distinctly drop of red cell precursors in the bone marrow.…”

Single-cell profiling of human bone marrow progenitors reveals mechanisms of failing erythropoiesis in Diamond-Blackfan anemia

“…However, inconsistent findings from human model cellular systems and cell lines (4,(14)(15)(16)) are yet to be reconciled, and it remains unclear whether additional mechanisms may contribute to erythroid failure in DBA (17). Furthermore, although the diagnostic criteria of DBA include presentation in infancy with virtually no mature bone marrow erythroblasts (EBs) (3), atypical presentations in later life with milder hematological manifestations are not uncommon (18)(19)(20)(21)(22). The mechanisms underpinning these heterogeneous clinical phenotypes are yet to be elucidated.…”

Functionally impaired RPL8 variants associated with Diamond–Blackfan anemia and a Diamond–Blackfan anemia‐like phenotype

“…This effect could also contribute to the pathogenicity of the p.S138F variant. We conclude that expression of the p.S138F variant in the DBA patient reported in a Japanese cohort (Wang et al, 2015) affects ribosome synthesis and results in a deficit -Shemer et al, 2016). Some patients are diagnosed later in life with mild anemia requiring no therapy (Gazda et al, 2008).…”