Shwachman-Diamond Syndrome

What causes Shwachman-Diamond syndrome

About 90% of people with SDS have variants in both copies of the SBDS gene, which helps cells build ribosomes, the machinery that makes proteins. This mainly affects rapidly dividing cells in the bone marrow and pancreas, and bone development. A small number of cases are caused by other genes (such as DNAJC21, EFL1 and SRP54).

SDS is autosomal recessive: both parents are usually healthy carriers, and each child has a 25% chance of being affected.

It is rare, estimated at about 1 in 75,000 to 1 in 170,000 births. After cystic fibrosis, it is one of the most common inherited causes of exocrine pancreatic insufficiency in children.

Symptoms

Pancreas and digestion

• Exocrine pancreatic insufficiency: bulky, greasy, pale, foul-smelling stools that may float
• Poor weight gain and failure to thrive in infancy
• Deficiency of fat-soluble vitamins A, D, E and K
• Pancreatic function often improves in about half of children by age 4, although enzyme levels remain reduced

Bone marrow

• Neutropenia: present at some point in almost all patients, may be constant or intermittent
• Frequent infections: ear infections, pneumonia, skin infections, mouth ulcers
• Anemia and low platelets in some patients
• Aplastic anemia (complete marrow failure) in a minority

Skeleton

• Short stature
• Metaphyseal dysplasia: abnormal growth at the ends of long bones, causing leg bowing or knock knees
• Narrow rib cage, which can cause breathing problems in newborns
• Osteoporosis later in life

Other features

• Developmental delay and learning difficulties in some children
• Liver enzyme elevation, usually mild
• Dental problems
• Skin eczema

Diagnosis

Diagnosis combines:

1. Evidence of pancreatic dysfunction: low fecal elastase, low serum trypsinogen or pancreatic isoamylase, or fatty stool tests
2. Evidence of bone marrow dysfunction: neutropenia on repeated blood counts, other low counts, and bone marrow examination
3. Genetic testing for SBDS and related genes
4. Exclusion of cystic fibrosis with a sweat chloride test, since both cause pancreatic insufficiency
5. Skeletal X-rays to look for typical bone changes

Treatment

There is no cure for SDS, except that stem cell transplant can replace the bone marrow. Care is coordinated by a team including hematology, gastroenterology, nutrition and orthopedics.

Nutrition

• Pancreatic enzyme replacement with meals and snacks
• Fat-soluble vitamin supplements (A, D, E, K)
• Dietitian support to ensure adequate calories and growth

Infection management

• Prompt assessment and antibiotics for fever when neutrophils are low
• G-CSF (granulocyte colony-stimulating factor) injections for severe neutropenia with recurrent serious infections
• Routine vaccinations

Blood and marrow monitoring

• Blood counts every 3 to 6 months
• Regular bone marrow examinations to detect early changes toward myelodysplastic syndrome or acute myeloid leukemia
• Blood or platelet transfusions if needed

Stem cell transplant

Hematopoietic stem cell transplantation is considered for severe bone marrow failure, myelodysplastic syndrome or leukemia. It does not correct the pancreatic or skeletal features.

Bones and growth

Monitoring growth and bone density, orthopedic care for skeletal problems, and vitamin D and calcium.

Outlook

Many people with SDS live into adulthood, especially with good nutrition and infection management. Pancreatic symptoms often improve in childhood. The main long-term concern is the risk of bone marrow failure and leukemia, which increases with age, making lifelong monitoring important. Genetic counseling helps families understand recurrence risk.

Frequently asked questions

What is Shwachman-Diamond syndrome?

It is a rare inherited disorder that affects the pancreas, bone marrow and bones. It causes poor digestion of fats, low blood counts (especially neutrophils), frequent infections, short stature, and an increased risk of bone marrow failure and leukemia.

What are the first signs of Shwachman-Diamond syndrome?

In infancy, the first signs are usually greasy, foul-smelling stools, poor weight gain despite feeding well, and repeated infections. Some babies have breathing difficulties from a narrow chest.

How is Shwachman-Diamond syndrome inherited?

It is usually autosomal recessive. Both parents carry one faulty copy of the SBDS gene without symptoms, and each of their children has a 25% chance of having SDS and a 50% chance of being a carrier.

How is Shwachman-Diamond syndrome treated?

Treatment includes pancreatic enzymes and vitamins for digestion and growth, prompt treatment of infections, G-CSF for severe neutropenia, transfusions if needed, and regular bone marrow checks. Stem cell transplant is used for marrow failure or leukemia.

What is the life expectancy with Shwachman-Diamond syndrome?

It varies widely. Many people live into adulthood with good care. Serious infections in childhood and bone marrow failure or leukemia later are the main threats, so regular monitoring and early treatment are essential.