The syndrome of pancreatic insufficiency and bone marrow dysfunction

Shwachman, Harry; Diamond, Louis K.; Oski, Frank A.; Khaw, Kon Taik

doi:10.1016/s0022-3476(64)80150-5

Cited by 533 publications

(263 citation statements)

References 30 publications

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“…3,35 Schwachman-Diamond syndrome SDS was first reported in 1964 by Schwachman et al in a group of 5 children being followed in a cystic fibrosis clinic at Harvard University. 40 SDS is an autosomal recessive disease, with an incidence estimated at 1 in 50 000 births, characterized by exocrine pancreatic insufficiency, ineffective hematopoiesis, and an increased risk of leukemia. Patients often present with steatorrhea and failure to thrive from the pancreatic insufficiency.…”

Section: Q؊ Syndromementioning

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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Section: Q؊ Syndromementioning

confidence: 99%

Ribosomopathies: human disorders of ribosome dysfunction

Narla

Ebert

2010

Blood

698

726

View full text Add to dashboard Cite

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“…[1][2][3][4][5][6] Additional clinical manifestations seen in some patients include short stature, variable immune dysfunction, delayed dentition and structural and functional abnormalities of the liver. 3,4,7,8 Patients with SDS are at an increased risk of developing aplastic anemia, myelodysplastic syndrome (MDS) and AML.…”

Section: Introductionmentioning

confidence: 99%

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman–Diamond syndrome

Bhatla

Davies

Shenoy

et al. 2008

Bone Marrow Transplant

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“…It was firstly described in 1960s and its estimated incidence is one per 75.000 live births [1][2][3]. Skeletal changes, growth failure, dental anomalies, immunological defects and recurrent infections are the other features of SDS.…”

Section: Introductionmentioning

confidence: 99%

Molecular Diagnosis of Shwachman-Diamond Syndrome Presenting with Pancytopenia at an Early Age: The First Report from Turkey

Gökçe

Tuncer

Çetin

et al. 2012

Indian J Hematol Blood Transfus

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A three-month-old boy presented with growth failure, skeletal abnormalities, otitis media and pancytopenia. Exocrine pancreatic insufficiency was confirmed by low levels of fecal elastase. He was diagnosed as Shwachman-Diamond syndrome by clinical and laboratory findings. The diagnosis was confirmed by sequence analysis for SBDS gene on chromosome seven revealing compound heterozygous mutation, which are c.258?2T-C and c.183-184TA-CT. Matched unrelated donor screening for hematopoietic stem cell transplantation was initiated. Unfortunately, he died of respiratory difficulty at 5 months of age. Our case is the youngest patient whose presumptive Shwachman-Diamond syndrome diagnosis was confirmed by molecular analysis.

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The syndrome of pancreatic insufficiency and bone marrow dysfunction

Cited by 533 publications

References 30 publications

Ribosomopathies: human disorders of ribosome dysfunction

Ribosomopathies: human disorders of ribosome dysfunction

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman–Diamond syndrome

Molecular Diagnosis of Shwachman-Diamond Syndrome Presenting with Pancytopenia at an Early Age: The First Report from Turkey

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