Shwachman Diamond Syndrome (SDS)

Individuals with SDS have poor food absorption (malabsorption) and low white blood cell counts (neutropenia). Most individuals are diagnosed in infancy or early childhood. Males and females are equally affected.

What are the major findings on physical examination

Short stature
Bone development malformations ("metaphyseal dysostosis," a specific finding seen on an x-ray)

What is the age at diagnosis?

SDS diagnosis is usually made within the first year of life, but newly diagnosed adults have been reported.

What is the natural progression of bone marrow failure in individuals with SDS?

Some individuals with SDS can live for years without bone marrow failure while others develop symptoms earlier.
Bone marrow failure means the number of blood cells is too low because the bone marrow has stopped producing enough mature cells.
Individuals typically start with low blood cell counts in white blood cells, and may progress to low counts in two or more types of blood cells (also known as aplastic anemia):
- Low red blood cell count (anemia)
- Low platelet count (thrombocytopenia)
- Low white blood cell count (leukopenia)

What types of cancer are individuals with SDS at higher risk of developing?

Leukemia (cancer of the blood and bone marrow)

How is SDS specifically diagnosed?

Individuals with SDS usually have a decrease in specific digestive enzymes (trypsinogen and isoamylase) produced by the pancreas, which can be measured by various laboratory tests or imaging methods:
- Reduced pancreatic enzymes in the blood
- Abnormal amounts of fat in the stool
- Small or fatty pancreas seen using an ultrasound or CT scan imaging of the pancreas
Bone marrow failure which is indicated by:
- Low neutrophils in blood on at least three occasions
- Possible low hemoglobin and/or platelets
Genetic testing

Genetics

SDS can be caused by genetic variants in the SBDS gene, which stands for Shwachman Bodian Diamond Syndrome. The disease is inherited in an autosomal recessive manner. This means that individuals need both copies of the gene variant to have SDS. It is unclear how abnormal genetic variants in this ribosome gene lead to the major signs and symptoms of SDS.
Other rare SDS -causing gene variants occur in: EFLI1 (recessive), DNAJC21 (recessive), and SRP54 (dominant).