Diamond-Blackfan anemia is a rare genetic hematologic disorder characterized by congenital abnormalities, marrow failure, and predilection to malignancy. The condition has a highly variable clinical presentation, attributable to deficiencies in ribosomal function that can lead to physical malformations including stunted growth, thumb irregularities, and craniofacial anomalies. In the past, treatment has mainly consisted of glucocorticoids and chronic transfusions, which may lead to substantial toxicity and long-term complications.1,2

In a review article published in the British Journal of Haematology, Marije Bartels, MD, PhD, and Marc Bierings, MD, of the department of pediatric hematology at the University Medical Center in the Netherlands summarized the current literature on Diamond-Blackfan anemia in children and provided recommendations to help guide clinical practice.

Geoffrey Cuvelier, MD, director of the pediatric blood and marrow transplant program at the University of Manitoba in Canada, told Hematology Advisor, “Inherited bone marrow failure syndromes such as Diamond-Blackfan anemia are rare, but [it is] important for general practitioners such as family doctors and pediatricians to have some understanding [of] the diagnostic workup.”

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Pathogenesis of Diamond-Blackfan Anemia

In recent years, advances in gene technology and laboratory techniques have greatly enhanced understanding of the molecular mechanisms underlying inherited bone marrow conditions such as Diamond-Blackfan anemia. Researchers have identified specific molecular defects in ribosome formation linked to distinct gene mutations that cause Diamond-Blackfan anemia. The current hypothesis is that these mutations result in defective erythropoiesis, ultimately leading to erythroid failure.

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The mutated genes that instigate ribosomal dysfunction encode proteins with several key functions in erythropoiesis. While the individual effects of many of these mutations are unknown, patients with Diamond-Blackfan anemia are at an increased risk for developing certain malignancies, including acute myeloid leukemia, myelodysplastic syndrome, colon carcinoma, and osteosarcoma. The majority of patients are diagnosed as early infants, and the disorder is often first recognized when they start showing symptoms of severe anemia.

“In patients, there are often clues that a bone marrow failure syndrome is present, including dysmorphic features and failure of cytopenias to improve over time,” Dr Cuvelier said.

Treatment of Diamond-Blackfan Anemia in Children

Although preclinical trials investigating potential therapies for Diamond-Blackfan anemia are underway, hematopoietic stem cell transplantation (HSCT) is the only curative therapy currently available. However, transplantation is usually only performed as salvage therapy because of the potential for severe toxicity, which can occur shortly after treatment or in the long term. In addition, HSCT is not first-line treatment because many patients have experienced spontaneous remission without treatment.