Patient #1 presented with pancytopenia without other system involvement, while patient #2 presented with severe neutropenia, anemia, and a bifid thumb. Neither patient had diarrhea or malabsorption. [scholars.northwestern.edu]

SDS may present with either malabsorption, or hematological problems. Rarely, SDS may present with skeletal defects, including severe rib cage abnormalities that lead to difficulty in breathing. [en.wikipedia.org]

At diagnosis, growth retardation was present in all patients, and all subjects showed pancreatic insufficiency. [doi.org]

Mild dysplastic features may be present. Severe dysplasia warrants consideration of MDS. [cancertherapyadvisor.com]

• Anemia

  Blood analysis shows neutropenia (absolute neutrophil count Differential diagnosis Differential diagnoses include cystic fibrosis, Pearson syndrome, Fanconi anemia, Johanson-Blizzard syndrome, Blackfan-Diamond anemia, celiac disease, and autosomal recessive [orpha.net]

  When he was 61/2 years old a severe aplastic anemia occured and he received several blood transfusions. Anemia recovered 6 months later. [journals.lww.com]

  increased HgF levels, thrombocytopenia Low serum isoamylase and trypsinogen Treatment and prognostic factors 25% develop aplastic anemia, 7% develop myelodysplastic syndrome or acute myeloid leukemia Supportive treatment (G-CSF, transfusions, pancreatic [pathologyoutlines.com]

  Anemia (low red blood cell counts) and thrombocytopenia (low platelet counts) may also occur. [en.wikipedia.org]

• Short Stature

  stature, and skeletal changes. [medical-dictionary.thefreedictionary.com]

  Growth retardation: More than 50% of patients are below the third percentile for height, and short stature appears to be unrelated to nutritional status. [en.wikipedia.org]

  […] dbo: abstract Shwachman–Diamond syndrome (SDS) or Shwachman–Bodian–Diamond syndrome is a rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature. [dbpedia.org]

  Lipomatosis of the pancreas found on MR and CT and the clinical findings pancytopenia, short stature, and recurrent infections are typical for Shwachman syndrome. [ncbi.nlm.nih.gov]

• Malnutrition

  Other rarer causes of pancreatic exocrine insufficiency include severe malnutrition, Pearson syndrome, Johanson-Blizzard syndrome and Jeune syndrome. [dx.doi.org]

  As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome. [ghr.nlm.nih.gov]

  Steatorrhea is noted in the first 6 months of life in about 50% of affected children and increases to 90% by the age of one. (5) Steatorrhea and malabsorption might lead to malnutrition and fat-soluble vitamin deficiency (A, D, E, K). (4) Hematological [signavitae.com]

  Thus, patients typically present in early infancy with malabsorption, steatorrhea, failure to thrive, and deficiencies of fat-soluble vitamins A, D, E, and K. [3, 4] Symptoms of malnutrition typically develop when more than 98% of pancreatic reserve is [emedicine.medscape.com]

• Increased Susceptibility to Infections

  Affected individuals with neutropenia may also have additional abnormalities believed to result from an increased susceptibility to infections. [rarediseases.org]

• Recurrent Otitis Media

  Although initially relating the beginning of her infections to mold exposure over the previous four years, the patient had experienced frequent respiratory tract infections since childhood, including recurrent otitis media, mastoiditis, and two episodes [journals.plos.org]

• Failure to Thrive

  Exocrine pancreatic insufficiency results in failure to thrive, growth retardation, and chronic steatorrhea. [orpha.net]

  Short stature Poor weight gain (“Failure to thrive”) Diarrhea Problems with bones (“metaphyseal dysostosis”, a specific finding seen on x-rays). Frequent infections How is SDS diagnosed? Blood tests are performed to document low white cells. [childrensmn.org]

  Early symptoms may include failure to thrive, feeding problems, and recurrent bacterial infections. Growth often remains below normal. Patients with Shwachman Diamond Syndrome have an increased risk of developing Leukemia. [butterflyguild.org]

  A likely toxic medullar effect of valproate acid therapy, given since one year for a syndromatic epilepsy, is discussed. 3° a one month baby EM.. . was admitted because of failure to thrive and one inguinal abcess. [journals.lww.com]

• Steatorrhea

  Pancreatic lipase secretion was assessed in 3 patients with steatorrhea and 5 without steatorrhea (73% of the surviving patients) using a sensitive assay which used maximum stimulation with colipase. [ncbi.nlm.nih.gov]

  Steatorrhea is noted in the first 6 months of life in about 50% of affected children and increases to 90% by the age of one. (5) Steatorrhea and malabsorption might lead to malnutrition and fat-soluble vitamin deficiency (A, D, E, K). (4) Hematological [signavitae.com]

  Exocrine pancreatic insufficiency results in failure to thrive, growth retardation, and chronic steatorrhea. [orpha.net]

  126:1157 ) Clinical features and diagnosis Additional clinical findings: intellectual disability, facial dysmorphism, dental anomalies, ichthyosis, thoracic deformities Often presents with infections at birth due to neutropenia, also malabsorption (steatorrhea [pathologyoutlines.com]

• Dental Caries

  These may include increased tooth decay (dental caries), mouth ulcers, and/or disease of the tissues that surround and support the teeth (periodontal disease). [rarediseases.org]

• Coxa Vara

  Skeletal manifestations include delayed bone age with marked carpal delay, broad cup-like anterior ribs, metaphyseal irregularities, and coxa vara with short femoral necks. [mirc.rsna.org]

  Michael has upwards of 10 specialists and battles chronic severe neutropenia, osteoporosis, coxa vara of his hips, kidney issues, growth delay, psychosocial issues, developmental delays, pain and high functioning autism. [chla.org]

  Coxa valga was present on the right and some broadening and coxa vara on the left. The ribs were a little shortened. Figure 2 Chest radiograph of UPN1 at referral for BMT aged 11 years. [bmcpediatr.biomedcentral.com]

  vara 0002812 Elevated hepatic transaminase High liver enzymes 0002910 Enlargement of the costochondral junction 0000920 Intellectual disability, mild Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [rarediseases.info.nih.gov]

• Mild Cognitive Impairment

  Mild cognitive impairments and variable degrees of development abnormalities may also be seen in patients with Shwachman-Diamond syndrome. [12, 13, 14, 15, 16] These patients have lower performance in most cognitive domains than age-matched controls. [emedicine.medscape.com]

On more extensive workup, the second infant proved to have methylmalonic aciduria and was treated. The mother and family were eventually exonerated. [the-medical-dictionary.com]

His inital chest X-ray was normal and an aggressive pulmonary workup revealed no evidence of pneumonia. His pulmonary function tests were not significantly different from his pretransplant evaluation. [nature.com]

The presence of congenital anomalies or other suggestive physical findings (see below) in a patient with marrow failure warrants further workup for potential inherited syndromes such as SDS. [cancertherapyadvisor.com]

January 2002 Accepted 19 February 2002 Published 24 May 2002 Issue Date 01 April 2002 DOI https://doi.org/10.1038/sj.ejhg.5200798 Keywords Shwachman-Diamond syndrome 7q11 fine mapping haplotype sharing TPST1 gene exclusion Further reading Diagnostic workup [doi.org]

• Delayed Bone Age

  Skeletal manifestations include delayed bone age with marked carpal delay, broad cup-like anterior ribs, metaphyseal irregularities, and coxa vara with short femoral necks. [mirc.rsna.org]

  Bone involvement is characterized by delayed bone age and maturation with metaphyseal dysplasia resulting in short stature, pectus carinatum, and generalized osteopenia. [orpha.net]

  Birth weight is often normal, but more than 50% of patients are still below the 3rd percentile for height when they are one year old. (8) All patients exhibit delayed bone age and delayed puberty. [signavitae.com]

Treatment for children with SDS includes: pancreatic enzyme supplementation, vitamin supplementation and nutrition monitoring prevention and/or treatment of infections correction of low blood counts when possible prevention of orthopedic deformities close [childrensmn.org]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

We watch your child closely and recommend the right treatments at the right time. At Seattle Children’s we offer these treatment options: Most children with SDS have trouble getting enough nutrients from their food. [seattlechildrens.org]

Our patients have access to advanced treatments and diagnosis, including DNA mutation identification and ongoing clinical trials investigating new treatments. [childrenshospital.org]

Prognosis Prognosis is variable. Life-threatening complications include bone marrow aplasia and leukemic transformation, and occasionally viral infections. [orpha.net]

Patients with severe bone marrow involvement may have a guarded prognosis. [ncbi.nlm.nih.gov]

MDS and AML in patients with SDS has a poor prognosis, with a survival rate of < 20%. Inborn conditions Rare reports of increase in spontaneous chromosomal breakage. [atlasgeneticsoncology.org]

Etiology SDS is caused in 95% of cases by mutations in the SBDS gene (7q11.22) encoding a ribosomal protein involved in ribosomal biogenesis and other cellular processes. [orpha.net]

Our findings provide insight into the etiology of the developmental defects that result from loss of dSbds function and further strengthen the hypothesis that small molecules that mimic the effects of eIF6 suppressor mutations may have utility in the [nyas.org]

Summary Epidemiology Worldwide prevalence is estimated at about 1/350,000 and birth-prevalence at around 1/200,000 live births. Clinical description SDS shows a variable clinical picture, even within families. [orpha.net]

Epidemiology of chronic pancreatitis: burden of the disease and consequences. United European Gastroenterol J. 2014 Oct;2(5):345-54. Available online at https://www.ncbi.nlm.nih.gov/pubmed/25360312. Accessed on 3/19/17. [labtestsonline.it]

Alter, MD, MPH From the Department of Pathology, University of Texas Medical Branch, Galveston, Tex (Dr Elghetany); and the Division of Cancer Epidemiology and Genetics, the National Cancer Institute, Bethesda, Md (Dr Alter) Arch Pathol Lab Med 2002;Vol [thedoctorsdoctor.com]

Rosenberg, PhD 2 1 Clinical Genetics Branch, National Cancer Institute, Rockville, Maryland 2 Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland The National Cancer Institute (NCI) Inherited [nyas.org]

Therefore, a younger SDS infant such as our patient is unlikely to develop diabetes through the same pathophysiological changes in the pancreas as those seen in CF-related diabetes. [care.diabetesjournals.org]

Studies to understand the pathophysiology of bone marrow failure are currently underway. [emedicine.medscape.com]

Shimamura A, Alter BP (2010) Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 24:101–122 PubMedCentral PubMed CrossRef Google Scholar 19. [link.springer.com]

Treatment for children with SDS includes: pancreatic enzyme supplementation, vitamin supplementation and nutrition monitoring prevention and/or treatment of infections correction of low blood counts when possible prevention of orthopedic deformities close [childrensmn.org]

A weekly dose of 2 micrograms/kg/day was able to maintain the absolute neutrophil count high enough (0.58-1.2 x 10(9)/L) to prevent suppurative infections. [ncbi.nlm.nih.gov]

Shimamura determined that SBDS also functions to stabilize the mitotic spindle and prevent genomic instability (Austin et al ., 2008). [fredhutch.org]

Standard prevention of graft versus host disease (GVHD) with ciclosporin ± methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T‐cell depletion was used in 17 and four patients respectively. [doi.org]