Contributions
Abstract: PB1468
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH - Biology & Translational Research
Background
Blackfan-Diamond Anemia (BDA) is a rare congenital bone marrow failure (BMF) syndrome characterized by selective aplasia of the erythroid progenitor lineage. Typically BDA is diagnosed within the first year of life, with the presentation of normochromic, microcytic anemia accompanied by reticulocytopenia. BDA is caused by inherited or de novo mutations in ribosomal proteins and is recognised as the first known human ribosomopathy. Symptoms are heterogenous, even between affected family members carrying the same mutations. Most often the genes involved are RPS19, RPS24, RPS 17, RPL35A and RPS 26. RPS 26 is responsible for 2.5-6% of DBA patients and to date 30-disease causing variants have been reported. Many of the patients affected present with clinical malformations, and there seems to be a correlation between the phenotype and genotype.
Aims
We describe a case of DBA presenting with heart failure secondary to a serious severe anemia.
Methods
A 3 month old male infant, due to poor feeding and marked paleness undertook a full blood count which revealed remarkable anemia (Hb 1.8 g/dL). The infant was born at 35w gestation age and admitted in NICU due to low birth weight and jaundice though phototherapy was not applied. In the newborn period the infant was feeding well and presented no respiratory distress. Prenatal history was unremarkable and there was no history of anemia. Physical examination revealed no dysmorphic features and normal appearing with no evident anomalies.
The infant was immediately transfused, however, due to deterioration of its clinical condition with gasping and cardiac failure accompanied by bradycardia, was transferred to PICU and eventually intubated. The infant presented kidney failure, with reduced diuresis and hypertension and received anti-hypertensive treatment. The reticulocyte index upon admission was 3.4 percent and all other hematologic parameters and bilirubin levels were normal. A peripheral smear showed the presence of all white blood cell lineages with normal morphology; platelets were increased and displayed variable size (small to large). Red blood cells were decreased and schistocytes, elliptocytes, spherocytes, and Heinz bodies were not present.
The infant had no signs of hemolysis and the presence of infectious etiologies or structural abnormalities was excluded-negative studies for HIV, parvovirus, toxoplasmosis, and cytomegalovirus infection. Since there was no compensatory reticulocytosis, a congenital anemia associated with BMF, such as Diamond Blackfan anemia, was suspected.
Results
Morphologic review of the bone marrow aspirate exhibited complete absence of the erythroid lineage with the presence of hemophagocytic islets. Taking under consideration the bone marrow morphology in conjunction with the low reticulocyte count, a Blackfan-Diamond analysis was performed for the RPS19, RPL11, RPL5 which was negative. Due to the high index of suspicion, whole exome sequencing was performed which revealed a nucleic substitution of c181+1del IG of the RPS26 gene. The mutation was in heterozygosis with a possible formation of a non functional proteic molecule and not described in literature. Upon confirmation of diagnosis, due to the age (<12m), the infant was commenced on regular transfusions in order to avoid side effects from the use of the corticosteroid treatment. The infant has moderate transfusional needs (approx. once every 3 months).
Conclusion
As the WES/NGS testing becomes more accessible, novel mutations can be identified providing the possibility of the gene therapy in the future.
Keyword(s): Anemia, Bone marrow failure, Pure red cell aplasia, RPS19
Abstract: PB1468
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH - Biology & Translational Research
Background
Blackfan-Diamond Anemia (BDA) is a rare congenital bone marrow failure (BMF) syndrome characterized by selective aplasia of the erythroid progenitor lineage. Typically BDA is diagnosed within the first year of life, with the presentation of normochromic, microcytic anemia accompanied by reticulocytopenia. BDA is caused by inherited or de novo mutations in ribosomal proteins and is recognised as the first known human ribosomopathy. Symptoms are heterogenous, even between affected family members carrying the same mutations. Most often the genes involved are RPS19, RPS24, RPS 17, RPL35A and RPS 26. RPS 26 is responsible for 2.5-6% of DBA patients and to date 30-disease causing variants have been reported. Many of the patients affected present with clinical malformations, and there seems to be a correlation between the phenotype and genotype.
Aims
We describe a case of DBA presenting with heart failure secondary to a serious severe anemia.
Methods
A 3 month old male infant, due to poor feeding and marked paleness undertook a full blood count which revealed remarkable anemia (Hb 1.8 g/dL). The infant was born at 35w gestation age and admitted in NICU due to low birth weight and jaundice though phototherapy was not applied. In the newborn period the infant was feeding well and presented no respiratory distress. Prenatal history was unremarkable and there was no history of anemia. Physical examination revealed no dysmorphic features and normal appearing with no evident anomalies.
The infant was immediately transfused, however, due to deterioration of its clinical condition with gasping and cardiac failure accompanied by bradycardia, was transferred to PICU and eventually intubated. The infant presented kidney failure, with reduced diuresis and hypertension and received anti-hypertensive treatment. The reticulocyte index upon admission was 3.4 percent and all other hematologic parameters and bilirubin levels were normal. A peripheral smear showed the presence of all white blood cell lineages with normal morphology; platelets were increased and displayed variable size (small to large). Red blood cells were decreased and schistocytes, elliptocytes, spherocytes, and Heinz bodies were not present.
The infant had no signs of hemolysis and the presence of infectious etiologies or structural abnormalities was excluded-negative studies for HIV, parvovirus, toxoplasmosis, and cytomegalovirus infection. Since there was no compensatory reticulocytosis, a congenital anemia associated with BMF, such as Diamond Blackfan anemia, was suspected.
Results
Morphologic review of the bone marrow aspirate exhibited complete absence of the erythroid lineage with the presence of hemophagocytic islets. Taking under consideration the bone marrow morphology in conjunction with the low reticulocyte count, a Blackfan-Diamond analysis was performed for the RPS19, RPL11, RPL5 which was negative. Due to the high index of suspicion, whole exome sequencing was performed which revealed a nucleic substitution of c181+1del IG of the RPS26 gene. The mutation was in heterozygosis with a possible formation of a non functional proteic molecule and not described in literature. Upon confirmation of diagnosis, due to the age (<12m), the infant was commenced on regular transfusions in order to avoid side effects from the use of the corticosteroid treatment. The infant has moderate transfusional needs (approx. once every 3 months).
Conclusion
As the WES/NGS testing becomes more accessible, novel mutations can be identified providing the possibility of the gene therapy in the future.
Keyword(s): Anemia, Bone marrow failure, Pure red cell aplasia, RPS19