A Case of Diamond Blackfan Anemia with Mutation in Ribosomal Protein S19

Abstract

Diamond Blackfan Anemia (DBA) is a rare disorder which presents with anemia in early infancy. This disorder is genetically and clinically heterogeneous in nature. The inheritance is mainly autosomal dominant. Approximately 25% of the cases are associated with craniofacial anomalies and some cases may end up in malignancy. The diagnosis is made by blood investigations, and bone marrow studies in which red cell precursors are reduced or absent. Screening for the mutations including those encoding for ribosomal proteins in the patient and the family members confirms the diagnosis. Human Leukocyte Antigen (HLA) matched hemopoietic stem cell transplantation is the treatment of choice. In other cases, corticosteroids and cyclosporine A have been tried. The haemoglobin level is maintained with packed red cell transfusion. We are presenting here a female baby who had anemia at birth and was brought to us at the age of 2 months. The diagnosis of DBA was made since the patient presented with anemia and showed reticulocytopenia, gross reduction in Red Blood Cell (RBC) count, and reduction in red cell precursors in the bone marrow. Genetic screening revealed mutation in ribosomal protein S19 (RPS19) gene in both the infant and the father.

A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia

“…The DBA database (Boria et al., , ) included 129 RPS19 mutations in 219 patients at its last update in 2010. We reviewed the literature to collect additional RPS19 mutations identified more recently and now have a total of 165 different RPS19 mutations reported in 313 DBA patients (Arbiv et al., ; Chae et al., ; Da Costa et al., ; Delaporta et al., ; Errichiello et al., ; Farrar et al., ; Gerrard et al., ; Ichimura et al., ; Konno et al., ; Kuramitsu et al., ; Landowski et al., ; Ozono et al., ; Pospisilova et al., ; Quarello et al., ; Smetanina et al., ; Solomon et al., ; Tsangaris et al., ; van Dooijeweert et al., ; Wang et al., ; Zhang et al., ). For our study, we selected only those variants for which there was no strong evidence of pathogenicity according to the genetic criteria outlined in Materials and Methods, and obtained 47 VUS reported in 122 patients (39% of RPS19‐mutated patients, approximately 10% of all DBA patients).…”

Anemia de Diamond Blackfan, un diagnóstico de exclusión

“…Estos criterios, hasta hace poco, seguían siendo la norma aceptada. (6) Es causada por mutaciones que afectan genes que codifican para proteínas ribosomales, inicialmente fue identificado RPS19, que codifica la proteína S19 (rpS19); y las mutaciones a otros genes que codifican proteínas ribosomales confirman la patología como un trastorno de biogénesis o función ribosomal, ratificado por la demostración de la haploinsuficiencia de RPS14 representado en la anemia macrocítica asociada con el síndrome de 5q-(1), un subtipo de síndrome mielodisplásico. (3) Aproximadamente el 50% de los pacientes tienen mutaciones que afectan un único alelo de los genes de proteínas ribosomales S19, L5, L11, o S26.…”

“…(1) La anemia responde hasta en un 70% de los casos a terapia con esteroides, aproximadamente el 40% de los afectados dependen de un programa de trasfusión a largo plazo hasta que se encuentra un donante apropiado para un trasplante de células madre hematopoyéticas e inclusive la patología puede resolver después de años de trasfusiones. La terapia de transfusión a menudo tiene que ser combinada con la terapia de quelación del hierro para evitar la hemosiderosis y sus consecuencias deletéreas (6). Según el registro de DBA de Norteamérica la tasa actual de supervivencia es de 75,1% y 4,8% a los 40 años de edad; los pacientes que no responden a los esteroides tienen una tasa más baja de supervivencia.…”