What is Shwachman-Diamond Syndrome?
Schwachman-Diamond syndrome (SDS) is a genetic disorder that is generally inherited, known for being the second major cause of exocrine pancreatic insufficiency, which is when the pancreas isn’t able to produce enough important enzymes, after cystic fibrosis. It’s usually recognized by a combination of three symptoms: issues with the pancreas not properly secreting enzymes, problems with the bones, and an inability of the bone marrow to function correctly. Sometimes, patients might also experience heart problems, issues with their immune system, and blood disorders. In most cases, about 90 percent, the patients have a specific mutation, or change, in the Shwachman-Bodian-Diamond syndrome (SBDS) gene located on the 7th chromosome.
What Causes Shwachman-Diamond Syndrome?
Shwachman-Diamond syndrome (SDS), a rare genetic condition, is caused by a mutation or change in a gene named SBDS, which is located on chromosome 7. A gene is a part of DNA and carries specific instructions to make proteins. This particular gene gives instructions for making a protein also called SBDS.
This SBDS protein is widely distributed and functions in different systems of the body. Apart from the SBDS gene, there is also a very similar gene, known as the SBDSP pseudogene, found very close to it on the same chromosome 7. Sometimes, these two locations on the chromosome can interact with each other, leading to a mutation or change in the SBDS gene. This change is what leads to Shwachman-Diamond syndrome.
Risk Factors and Frequency for Shwachman-Diamond Syndrome
This disorder is quite rare, with only one case reported per 75,000 people. It typically affects infants. People with this disorder can often live into their thirties and forties. It affects more males than females, with a ratio of 1.7 males for every female affected.
Signs and Symptoms of Shwachman-Diamond Syndrome
Shwachman-Diamond Syndrome (SDS) is a condition that often goes unnoticed in the larger population because its symptoms can be vague. This can occur at any stage in life but mostly shows up early on. The most common symptoms are linked to the digestive system and blood disorders, with other signs being less frequent. General symptoms include difficulty digesting food and absorbing nutrients, and a lack of vitamins that are normally absorbed from fats. As people grow older, these symptoms normally get better.
Blood disorders common in SDS include a decreased count of white blood cells, which can cause recurring viral and bacterial infections such as sinusitis, pneumonia, bone infection, and blood infection. People with SDS can also experience bleeding, which can sometimes be severe, due to a reduction in platelets. Furthermore, anemia is seen in nearly 80% of patients, characterized by larger than normal or regular-sized red blood cells.
People with SDS can also show signs of bone abnormalities. These can include shorter height, abnormal rib cage, hip dislocation, and deformities in the spine and fingers.
In addition to these physical symptoms, SDS can also affect a person’s mental capabilities. Such issues can include intellectual disability, reduced attention span, difficulty with decision-making and planning, and problems with hand-eye coordination. Behavioural changes are also reported in children with SDS.
Testing for Shwachman-Diamond Syndrome
According to the latest guidelines, diagnosing Shwachman-Diamond syndrome (SDS), a rare genetic condition, requires the presence of blood irregularities and decreased pancreas function. However, it’s important to rule out other causes of bone marrow and pancreas issues.
For those who might have decreased pancreas function, a test measuring the fat in stool over 72 hours is typically performed. Two substances, trypsinogen and isoamylase, present in the pancreas can aid in the diagnosis. The levels of trypsinogen can only be measured before a child turns three years old, as these levels start to rise thereafter. Isoamylase levels, on the other hand, always remain low. SDS can be distinguished from cystic fibrosis, another condition that affects similar organs, by a sweat test that produces normal results in SDS patients.
Regular blood tests can provide useful information about possible decreases in certain types of blood cells, a condition called cytopenias. Patients with SDS need regular blood checks to detect any early signs of progression to diseases affecting the bone marrow or a form of blood cancer called acute myelogenous leukemia (AML).
Genetic testing looking for mutations in the SBDS gene can definitively confirm the diagnosis in about 90% of SDS cases. Once the diagnosis is confirmed, a bone marrow biopsy (a test where a small amount of bone marrow is removed for testing), checking the liquid part of the bone marrow, and other tests looking at cells, along with an in-depth study of the entire skeleton, are recommended.
If there’s any concern about a patient having learning or thinking problems, they should be referred to a specialist for further evaluation.
Treatment Options for Shwachman-Diamond Syndrome
If you’ve been diagnosed with Shwachman-Diamond syndrome (SDS), your doctor may start you on pancreatic enzyme replacement therapy. This treatment has been shown to be effective for many SDS patients. You’ll also need regular testing (every 6 to 12 months) to monitor levels of vitamins that dissolve in fat, replacing them as needed. As SDS improves over time in some patients, the use of pancreatic enzymes might not be necessary indefinitely. Additionally, it’s beneficial for you to work with a certified dietitian to help manage your diet and perform regular checks on your weight and height to track your growth over time.
For SDS patients who are struggling with anemia (low red blood cell count) or thrombocytopenia (low platelet count), transfusions are often necessary. This involves receiving additional red blood cells or platelets to help your body function properly. If you need a lot of red blood cell transfusions, your doctor might also recommend a treatment called iron chelation to help remove excess iron from your body.
Infections are a serious concern for SDS patients due to leukopenia, a condition where white blood cells are low. If you get an infection, it’s important to start antibiotics right away. In some cases of severe leukopenia, or if you get infections often, your doctor might recommend a drug called Granulocyte Colony-Stimulating Factor (G-CSF) which helps your body produce more white blood cells.
Because this is a rare disease, regular checks with a blood specialist (a hematologist) every 3 to 4 months are necessary to identify potential problems early. Despite the need for such monitoring, remember there’s no specific chemotherapy that’s been approved for SDS. Current chemotherapy can only control, but not cure, the disease. A procedure called a hematopoietic stem cell transplant (HSCT) is currently the only known curative treatment. Survival rates after HSCT tend to be better for patients with bone marrow failure compared to those with leukemia.
Remember, SDS patients can experience more severe side effects from chemotherapy and HSCT than people without SDS. These potentially include infections, persistent aplasia, heart toxicity, and kidney failure.
If you’ve been diagnosed with SDS, it’s necessary to be aware of your bone health. Regular checks for a condition called osteoporosis (which causes weak and brittle bones) are recommended, and maintaining proper Vitamin D levels are important for bone health. Regular check-ups of your bones especially if you had problems initially can also help track and manage the progression of the disease.
Last but certainly not least, it’s important for SDS patients, especially children between the ages of 5 and 18, to undergo regular neuropsychological evaluations. This will help to assess brain development and ensure that appropriate support is provided.
What else can Shwachman-Diamond Syndrome be?
Here are some health conditions that might be worth looking into:
- Cystic fibrosis
- Pearson syndrome
- Pancreatic agenesis
- Johanson-Blizzard syndrome
- Cartilage-hair hypoplasia
