Anaemia of Infancy and Early Childhood

Josephs, H. W.

doi:10.1097/00005792-193615030-00001

Cited by 145 publications

(53 citation statements)

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“…This patient resembles in most aspects the pure red cell anemia first mentioned by Josephs (1936) and later described in more detail by Diamond & Blackfan (1938). In an extensive review, Diamond et al (1961) emphasized the possibility of spontaneous remissions even after many years of transfusions, and remarked on the significant correlation between the duration of the disease before therapy and its response to steroids.…”

Section: Commentsupporting

confidence: 74%

Congenital Hypoplastic Anaemia with Transfusion Siderosis

Tucker¹,

Pinckney²

1965

Proceedings of the Royal Society of Medicine

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Section: Commentsupporting

confidence: 74%

Congenital Hypoplastic Anaemia with Transfusion Siderosis

Tucker¹,

Pinckney²

1965

Proceedings of the Royal Society of Medicine

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“…DBA was originally described by Josephs in a review of anemia in infancy and childhood in 1936 12 and later categorized by Diamond and Blackfan as a congenital hypoplastic anemia. 12,13 The disorder is characterized by anemia, macrocytosis, reticulocytopenia, and a selective decrease or absence of erythroid precursors in an otherwise normocellular bone marrow.…”

Section: Diamond-blackfan Anemiamentioning

confidence: 99%

“…12,13 The disorder is characterized by anemia, macrocytosis, reticulocytopenia, and a selective decrease or absence of erythroid precursors in an otherwise normocellular bone marrow. 9 The incidence is estimated to be 4 to 5 cases per million live births, and there are 595 patients currently registered in the Diamond-Blackfan Anemia Registry of North America (A. Vlachos, Schneider Children's Hospital, Division of Hematology/ Oncology, personal written communication, January 2010).…”

Section: Diamond-blackfan Anemiamentioning

confidence: 99%

Ribosomopathies: human disorders of ribosome dysfunction

Narla

Ebert

2010

Blood

698

726

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Ribosomopathies compose a collection of disorders in which genetic abnormalities cause impaired ribosome biogenesis and function, resulting in specific clinical phenotypes. Congenital mutations in RPS19 and other genes encoding ribosomal proteins cause Diamond-Blackfan anemia, a disorder characterized by hypoplastic, macrocytic anemia. Mutations in other genes required for normal ribosome biogenesis have been implicated in other rare congenital syndromes, SchwachmanDiamond syndrome, dyskeratosis congenita, cartilage hair hypoplasia, and Treacher Collins syndrome. In addition, the 5q؊ syndrome, a subtype of myelodysplastic syndrome, is caused by a somatically acquired deletion of chromosome 5q, which leads to haploinsufficiency of the ribosomal protein RPS14 and an erythroid phenotype highly similar to Diamond-Blackfan anemia. Acquired abnormalities in ribosome function have been implicated more broadly in human malignancies. The p53 pathway provides a surveillance mechanism for protein translation as well as genome integrity and is activated by defects in ribosome biogenesis; this pathway appears to be a critical mediator of many of the clinical features of ribosomopathies. Elucidation of the mechanisms whereby selective abnormalities in ribosome biogenesis cause specific clinical syndromes will hopefully lead to novel therapeutic strategies for these diseases. Identification of ribosomal abnormalities in human diseaseIn 1999, Draptchinskaia et al reported recurrent mutations in a ribosomal protein gene, RPS19, in patients with Diamond-Blackfan anemia (DBA), a rare congenital bone marrow failure syndrome with a striking erythroid defect. 1 Since that initial discovery, mutations in a number of ribosomal proteins have been identified in up to 50% of patients with DBA. Moreover, other congenital syndromes have been linked to defective ribosome biogenesis, including Schwachman-Diamond syndrome (SDS), X-linked dyskeratosis congenita (DKC), cartilage hair hypoplasia (CHH), and Treacher Collins syndrome (TCS). 2 In the 5qϪ syndrome, a subtype of adult myelodysplastic syndrome, acquired haploinsufficiency for RPS14 resulting from an interstitial chromosomal deletion causes a severe refractory anemia. 3 Each of these disorders is associated with specific defects in ribosome biogenesis, which cause distinct clinical phenotypes, most often involving bone marrow failure and/or craniofacial or other skeletal defects. The disorders of ribosome dysfunction have become collectively known as ribosomopathies. Overview of ribosome biogenesisThe eukaryotic ribosome is composed of 40S and 60S subunits, which associate to form the translationally active 80S ribosome. This process requires the coordinated synthesis of 4 ribosomal RNAs (rRNAs), approximately 80 core ribosomal proteins, more than 150 associated proteins, and approximately 70 small nucleolar RNAs (snoRNAs). 4,5 The 40S subunit contains 18S rRNA and the 60S subunit contains 28S, 5.8S, and 5S rRNAs. In eukaryotes, assembly of rRNA and ribosomal proteins, along with assoc...

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“…Diamond Blackfan anemia (DBA) was first described as a disorder of impaired red blood cell production in children [1,2]. While most of the DBA cases are diagnosed in early infancy, a recent case report reveals that DBA can occur during fetal development.…”

Section: Introductionmentioning

confidence: 99%

Functional Links Between Glucocorticoids and Cytokines In DBA

2015

J Paediatr Child Care

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Diamond Blackfan anaemia (DBA) is a red blood cell aplasia characterized by erythropoietic defects as well as congenital anomalies. Forty percent of patients with DBA are treated with glucocorticoid steroids, which remain the mainstay of treatment in DBA. Many advances in the understanding of the physiological role of the glucocorticoid receptor have been made since the first introduction of glucocorticoids to the clinic, but their mechanism of action in the treatment of DBA is still under investigation. This review is intended to summarize the mechanism of glucocorticoid action specifically as related to erythropoiesis, focusing on the functional links between glucocorticoids and cytokines. IntroductionDiamond Blackfan anemia (DBA) was first described as a disorder of impaired red blood cell production in children [1,2]. While most of the DBA cases are diagnosed in early infancy, a recent case report reveals that DBA can occur during fetal development. This suggests that severely affected DBA fetus likely die to hydrops fetalis and result in undiagnosed miscarriages [3]. This disorder results from a cellular defect in which erythroid progenitors are highly sensitive to death by apoptosis, leading to erythropoietic failure [4]. The etiology of DBA has been the subject of continuous discussions, and while the early success of treatment with glucocorticoids (GCs) in 1951 [5] led to the idea that the pathogenesis of DBA could have an immunologic basis [6], it is now accepted that DBA is in fact a member of a rare group of genetic disorders.Approximately 50% of DBA patients have a single mutation in a gene encoding a ribosomal protein, which indicates that DBA is associated with a disorder of ribosome biogenesis and/or function [4]. The pronounced erythroid defect suggests that erythroid progenitors may express specific mRNAs that are hypersensitive to the decreased translation capacity [7]. Twenty-five percent of patients have a mutation in the ribosomal protein S19 (RPS19) gene [8], and two independent studies have demonstrated that over expression of the RPS19 transgene increases the number of erythroid colonies in RPS19 deficient hematopoietic progenitor cells in vitro [9,10]. In a mouse model of DBA, a high expression of RPS19 can rescue the erythroid development, and the corrected DBA cells show a survival advantage in vivo [11]. As zebrafish hematopoietic regulation is conserved with mammals, zebrafish models have also been reported to be useful in studying DBA [12][13][14], recapitulating many aspects of the DBA phenotype, including hematopoietic specific defects and p53 activation [14]. The list of genes that are mutated in DBA has been updated in 2013, to include ten ribosomal genes and one transcriptional regulator: RPS19, RPS24, RPS17, RPL35A, RPL5, RPL11, RPS7, RPS10, RPS26, RPL26, and GATA1 [15].More than 50 years after their introduction to the clinic, GCs are still the most effective drugs used in DBA. Nevertheless, the reported side effects of GCs include decreased growth velocity in infants...

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Anaemia of Infancy and Early Childhood

Cited by 145 publications

References 0 publications

Congenital Hypoplastic Anaemia with Transfusion Siderosis

Congenital Hypoplastic Anaemia with Transfusion Siderosis

Ribosomopathies: human disorders of ribosome dysfunction

Functional Links Between Glucocorticoids and Cytokines In DBA

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