Schwachman-Diamond syndrome

Shwachman–Diamond syndrome (SDS), is a rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities and short stature. 

It is the second most common cause of exocrine pancreatic insufficiency in children, after cystic fibrosis.

An autorecessive disorder.

The gene that is mutated in this syndrome, SBDS lies on the long arm of chromosome 7 at cytogenetic position 7q11.

Five-year survival rate 64%.

Frequency 122,600

 Is thought to have an estimated incidence of 1 in 75,000 people.

Deaths 21,650

The main characteristics of the syndrome are exocrine pancreatic dysfunction, hematologic abnormalities and growth retardation.

Hematologic abnormalities: neutropenia is the most common hematological finding, with risk of developing severe recurrent infections that may be life-threatening. 

Anemia and thrombocytopenia may also occur. 

Bone marrow is typically hypocellular.

There is maturation arrest in the myeloid lineages that give rise to neutrophils, macrophages, platelets and red blood cells. 

Patients may have progressive marrow failure or transform to acute myelogenous leukemia.

Pancreatic exocrine insufficiency in  Shwachman–Diamond syndrome arises due to a lack of acinar cells that produce digestive enzymes. 

These cells in the pancreas are extensively depleted and replaced by fat. 

With pancreatic exocrine insufficiency the lack of pancreatic digestive enzymes leaves patients unable to digest and absorb fat. 

Growth retardation occurs: more than 50% of patients are below the third percentile for height, and short stature appears to be unrelated to nutritional status. 

45%-50% of patients with Schwachman-Diamond syndrome have metaphyseal dysostosis, thoracic dystrophy, and costochondral thickening.

Other skeletal abnormalities include metaphyseal dysostosis (45% of patients), thoracic dystrophy (rib cage abnormalities in 46% of patients) and costochondral thickening (shortened ribs with flared ends in 32% of patients). 

Skeletal problems are variable with 50% affected siblings from the same family discordant for clinical presentation or type of abnormality. 

Most patients with the SD syndrome have radiographic osseous changes, the many  are subclinical.

Other features seen in SD syndrome include mild hepatic dysfunction, and increased frequency of infections.

The SBDS gene resides in a block of genomic sequence that is locally duplicated on the chromosome: The second copy contains a non-functional version of the SBDS gene that is 97% identical to the original gene.

The second copy of the gene has accumulated inactivating mutations over time, and is considered to be a pseudogene.

75% of disease-associated mutations are the result of gene conversion.

Two gene conversion mutations predominate in SDS patients. 

The SBDS gene is expressed in all tissues and encodes a protein of 250 amino acid residues. 

The  SBDS protein may be involved in an aspect of cellular RNA metabolism or ribosome assembly or function. 

SBDS in RNA metabolism or ribosome assembly or function is supported by its localization to the nucleolus, the nuclear subdomain where these processes occur. 

Cells from SDS patients were shown to have a defect in assembly of ribosome subunits.

Diamond–Blackfan anemia, X-linked dyskeratosis congenita, and cartilage–hair hypoplasia are three diseases that may also be linked to defective ribosome function. 


Initially, the clinical presentation of SDS may appear similar to cystic fibrosis. 

There is  a normal chloride in sweat test, and the fecal elastase as a marker of pancreatic function will be reduced. 

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. 

Diagnosis is generally based on evidence of exocrine pancreatic dysfunction and neutropenia. 

Skeletal abnormalities and short stature are characteristics that support the diagnosis. 

The gene responsible for the disease has been identified and genetic testing is available.


Pancreatic exocrine insufficiency may be treated through pancreatic enzyme supplementation

Skeletal abnormalities may require surgical intervention. 

Neutropenia may be treated with granulocyte-colony stimulating factor (GCSF) to boost peripheral neutrophil counts. 

Signs of progressive marrow failure may warrant bone marrow transplantation (BMT). 

SDS patients have an elevated occurrence of BMT-related adverse events, including graft-versus-host disease (GVHD) and toxicity relating to the pre-transplant conditioning regimen. 

The goals of therapy for SDS is to reduce the risk of bone marrow failure and halt the progression of malignant transformation toward myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), the most detrimental complications of SDS. 

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