Shwachman-Diamond syndrome: Year of the Zebra

Shwachman-Diamond syndrome, or SDS, is a rare genetic condition that primarily affects the bones, pancreas, and bone marrow. Most cases result from alterations in the SBDS gene, which affects the assembly of cell organelles called ribosomes. Ribosomes are essential to maintain cell function, and in SDS, ribosomal function is altered, causing changes in multiple body systems. SDS is inherited in an autosomal recessive pattern, meaning an individual with SDS inherits two altered genes, one from each parent.

Now, signs and symptoms of SDS are variable. If the bones are involved, individuals may have a short stature and skeletal changes like a short, flared rib cage or slowed ossification, or the formation of new bones.

SDS can also cause a decrease in pancreatic function, leading to a decrease in digestive enzymes that break down fat and protein, causing malabsorption. If left untreated, this can lead to decreased weight gain, failure to thrive, and steatorrhea, or fat-containing stools. However, decreased pancreatic function may improve as individuals age.

Decreased bone marrow function ranges from mild to severe. It can result in low blood cell counts particularly involving neutrophils, red blood cells, and platelets. The most common is low levels of neutrophils, also known as neutropenia. Neutropenia increases susceptibility to bacterial infections, leading to an increased risk of infections.

Low red blood cell counts, or anemia, can cause fatigue, pallor, and shortness of breath; and low platelet counts, or thrombocytopenia, can increase the risk of bleeding from minor injuries. Rarely, individuals with SDS may develop acute leukemia, or cancer of the blood; or other blood-related disorders, like myelodysplastic syndrome.

Diagnosis of SDS is suspected in individuals with symptoms of decreased pancreatic and bone marrow function. Laboratory tests involve a complete blood count, pancreatic enzyme levels, and a blood smear. Additionally, a bone marrow biopsy, which involves removing a small amount of bone filled with marrow for analysis, may be performed to rule out other conditions. In suspected cases, confirmation can be done through genetic testing.