Shwachman-Diamond syndrome (SDS) is a rare genetic disorder caused primarily by mutations in a specific gene called SBDS. This gene plays a crucial role in the normal functioning of cells, especially those involved in the bone marrow and pancreas. When the SBDS gene is mutated, it disrupts the production and maintenance of healthy blood cells and the proper functioning of the pancreas, leading to the characteristic features of SDS.
The SBDS gene mutation affects the body’s ability to produce enough healthy white blood cells, red blood cells, and platelets because it impairs bone marrow function. Bone marrow is the tissue inside bones responsible for making blood cells. In SDS, the bone marrow does not work properly, resulting in bone marrow dysfunction or failure. This leads to a weakened immune system, anemia, and problems with blood clotting.
In addition to bone marrow issues, SDS causes pancreatic insufficiency. The pancreas normally produces enzymes necessary for digestion, especially of fats and proteins. In SDS, the pancreas does not produce enough of these enzymes, leading to difficulties in digesting food and absorbing nutrients. This can cause poor growth and nutritional deficiencies in affected individuals.
Besides the SBDS gene, other genetic factors may contribute to the syndrome, but SBDS mutations are the most common cause. SDS is inherited in an autosomal recessive pattern, meaning a child must inherit two defective copies of the gene—one from each parent—to develop the syndrome. Parents who carry one mutated gene copy typically do not show symptoms but can pass the mutation to their children.
The exact mechanism by which SBDS mutations cause the symptoms of SDS involves problems with ribosome function. Ribosomes are the cell’s protein factories, and SBDS is involved in ribosome assembly and stability. When ribosomes do not function properly, cells, especially rapidly dividing ones like those in bone marrow and the pancreas, cannot produce proteins efficiently, leading to cell dysfunction and the clinical features of SDS.
SDS also affects the skeleton, causing abnormalities such as delayed bone growth and skeletal malformations. These arise because the mutation impacts cells involved in bone development and maintenance.
In summary, Shwachman-Diamond syndrome is caused by inherited mutations in the SBDS gene, which impair ribosome function, leading to bone marrow failure, pancreatic insufficiency, and skeletal abnormalities. The syndrome’s genetic nature means it runs in families, and its effects stem from the critical role of the SBDS gene in maintaining healthy cell function in multiple organ systems.
