Draft consensus guidelines for diagnosis and treatment of Shwachman-Diamond syndrome

The Hospital For Sick Children, University of Toronto, Ontario, Canada.
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 12/2011; 1242(1):40-55. DOI: 10.1111/j.1749-6632.2011.06349.x
Source: PubMed


Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic exocrine insufficiency and bone marrow failure, often associated with neurodevelopmental and skeletal abnormalities. Mutations in the SBDS gene have been shown to cause SDS. The purpose of this document is to provide draft guidelines for diagnosis, evaluation of organ and system abnormalities, and treatment of hematologic, pancreatic, dietary, dental, skeletal, and neurodevelopmental complications. New recommendations regarding diagnosis and management are presented, reflecting advances in understanding the genetic basis and clinical manifestations of the disease based on the consensus of experienced clinicians from Canada, Europe, and the United States. Whenever possible, evidence-based conclusions are made, but as with other rare diseases, the data on SDS are often anecdotal. The authors welcome comments from readers.

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    • "A diagnosis of SDS was rendered based on established clinical criteria of (1) a hematological cytopenia of any given lineage on at least 2 occasions over at least 3 months and (2) exocrine pancreas dysfunction [26]. Bone abnormalities supported the diagnosis. "
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    ABSTRACT: Background Shwachman–Diamond syndrome (SDS) is an autosomal recessive ribosomopathy caused mainly by compound heterozygous mutations in SBDS. Structural variation (SV) involving the SBDS locus has been rarely reported in association with the disease. We aimed to determine whether an SV contributed to the pathogenesis of a case lacking biallelic SBDS point mutations. Case presentation Whole exome sequencing was performed in a patient with SDS lacking biallelic SBDS point mutations. Array comparative genomic hybridization and Southern blotting were used to seek SVs across the SBDS locus. Locus-specific polymerase chain reaction (PCR) encompassing flanking intronic sequence was also performed to investigate mutation within the locus. RNA expression and Western blotting were performed to analyze allele and protein expression. We found the child harbored a single missense mutation in SBDS (c.98A > C; p.K33T), inherited from the mother, and an SV in the SBDS locus, inherited from the father. The missense allele and SV segregated in accordance with Mendelian expectations for autosomal recessive SDS. Complementary DNA and western blotting analysis and locus specific PCR support the contention that the SV perturbed SBDS protein expression in the father and child. Conclusion Our findings implicate genomic rearrangements in the pathogenesis of some cases of SDS and support patients lacking biallelic SBDS point mutations be tested for SV within the SBDS locus.
    BMC Medical Genetics 06/2014; 15(1):64. DOI:10.1186/1471-2350-15-64 · 2.08 Impact Factor
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    • "All these findings were present in this current case. Approximately 80% of patients have high levels of hemoglobin F(8). Bone marrow disease can progress to aplastic anemia, myelodysplastic syndrome or acute myeloid leukemia(1,7). "
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    ABSTRACT: Herein the first molecular diagnosis of a Brazilian child with Shwachman-Diamond Syndrome is reported. A 6-year-old boy was diagnosed with cystic fibrosis at the age of 15 months due to recurrent respiratory infections, diarrhea and therapeutic response to pancreatic enzymes. Three sweat tests were negative. At the age of 5 years, he began to experience pain in the lower limbs, laxity of joints, lameness and frequent falls. A radiological study revealed metaphyseal chondrodysplasia. A complete blood cell count showed leukopenia (leukocytes: 3.1-3.5 x 10(3)/µL), neutropenia (segmented neutrophils: 15-22%), but normal hemoglobin, hematocrit and platelet count. A molecular study revealed biallelic mutations in the Shwachman-Bodian-Diamond Syndrome gene (183-184TA-CT K62X in exon 2 and a 258+2T-C transition) confirming the diagnosis of Shwachman-Diamond Syndrome. A non-pathologic, silent nucleotide A to G transition at position 201 was also found in heterozygosis in the Shwachman-Bodian-Diamond Syndrome gene. This is the first report to describe a Brazilian child with molecular diagnosis of Shwachman-Diamond Syndrome, a rare autosomal recessive disorder characterized by exocrine pancreatic insufficiency, intermittent or persistent neutropenia and skeletal changes. Other characteristics include immune system, hepatic and cardiac changes and predisposition to leukemia. Recurrent bacterial, viral and fungal infections are common. The possibility of Shwachman-Diamond Syndrome should be kept in mind when investigating children with a diagnosis of cystic fibrosis and normal sweat tests.
    Revista Brasileira de Hematologia e Hemoterapia 04/2013; 35(4):290-292. DOI:10.5581/1516-8484.20130058
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    ABSTRACT: Editorial The 12th EFLM (former EFCC) Continuous Postgraduate Course in Clinical Chemistry: New Trends in Classification, Diagnosis and Management of Gastrointestinal Diseases The Croatian Society of Medical Biochemists and Slovenian Association for Clinical Chemistry, together with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM), organized in 2012 the 12th postgraduate weekend course entitled 'New Trends in Classification, Diagnosis and Management of Gastrointestinal diseases (GID)’. The Course is an advance study course in the frame of the Inter-University Centre (IUC) studies Dubrovnik promoting continuing postgraduate education of professionals also in clinical chemistry and laboratory medicine. The diploma of the IUC is recognized world wide. The Course is held under the auspices of Internal Federation of Clinical Chemistry and Laboratory Medicine (IFCC). In this book the state-of-the-art on gastrointestinal classification and epidemiology as well as new approach to diagnosis and management of GID is presented by well-known experts. These renowned experts in different fields have tried to cover the clinical and laboratory aspects of gastrointestinal diseases with the accent to gastrointestinal nutrition-related disease, gastrointestinal disease in children, chronic gastrointestinal diseases and gastrointestinal oncology. Integrated knowledge of the authors and the material prepared by these experts is intended to provide updated information of supreme quality to the reader interested in the field. The book contains two articles published in the Journal Biochemia Medica by generous permission of the Editor-in-Chief and Publisher of the journal. Elizabeta Topić Zagreb, November 2012
    Edited by Elizabeta Topić, Ian Watson, Evgenija Homšak, Jasna Leniček Krleža, 01/2012; Medicinska Naklada., ISBN: 978-953-176-593-0
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