What Is Shwachman-Diamond Syndrome

There are so many health conditions out there, that present with similar signs and symptoms that sometimes it can get really confusing and accurate diagnosis is vital for correct treatment prescription.One such disease is Schwachman-Diamond Syndrome known as SDS. 

Schwachman-Diamond Syndrome is a rare genetic disorder caused by a mutation in the SBDS gene. Its main characteristics are exocrine pancreatic insufficiency, bone marrow failure, short stature, malabsorption, etc.

As there is no cure for SDS and there are certain complications coming with it, the treatment options for this disease offer ways to manage such complications and, therefore, ease the everyday life of the patients.

Schwachman-Diamond Syndrome (SDS) can be described as a rare genetic condition considered to be inherited in an autosomal recessive fashion. There are two possible ways of inheritance of the SBDS gene (the mutated gene in SDS).¹ In simpler words, this means that both parents must be carriers of the faulty gene, with a 50% probability for their offspring to be carriers of the faulty gene and 25% or 1 in 4 that their child would have Schwachman-Diamond Syndrome (SDS); or if one parent is suffering from the condition and the other one does not contain the faulty gene, there is 50% chance that their children would be carriers of the disease.

The incidence of SDS is thought to be approximately 1 in 76,000 people, with the estimated ratio of males to females being 1.7:1, respectively. People with SDS have been found to have a 15%-25% higher chance of developing leukaemia (white blood cell cancer) than the general population.

Symptoms and characteristics of schwachman-diamond syndrome

Schwachman-Diamond Syndrome can be recognised via the observation of certain health-related characteristics such as:

• Pancreatic exocrine insufficiency
• Bone marrow failure
• Neurodevelopmental abnormalities
• Bone abnormalities
• Short stature
• Malabsorption
• Malnutrition
• Recurrent infections

Pancreatic dysfunction is usually diagnosed within the first six months or up to the first year of age (~90% of the patients).  Different ways to test for it are:

• Low levels of pancreatic isoamylase and cationic trypsinogen in the blood
• Abnormal faecal fat in faeces

This condition can affect multiple organ systems, the most common ones being:²

• Bone marrow
• Pancreas
• Body skeleton
• Liver, kidney, teeth, brain, and immune system

Hepatomegaly can be a common indication of SDS, especially in young children and babies (~75%). This is the elevation of liver enzymes, where usually normal levels restore with age.

Haematological (blood) abnormalities noticed in SDS patients can also aid in the diagnosis of the condition.

• Neutropenia is the most common haematological abnormality noticed. This is the reduced quantity of a specific type of white blood cell (neutrophil) in the patient's blood serum. Neutropenia is diagnosed when neutrophils are less than 1,500 neutrophils per mm3 for three or more measurements taken over a period of three months or longer.
• Anaemia is also a frequent complication. It is characterized by a lower concentration of haemoglobin in the blood, which is a molecule that reacts with and carries oxygen, which gives the blood its red appearance and supplies the body with oxygen.
• Thrombocytopenia is another haematological complication that can be observed by a lower than 150,000 platelet count per mm3.

Although most infants tend to not show signs of SDS, the ones who do have symptoms of early presentation such as life-threatening infections and asphyxiating thoracic dystrophy which is the result of altered bone structure of the chest, are observed as a narrow, bell-shaped chest. Other symptoms include bone marrow failure and aplastic anaemia (when the bone marrow is not able to produce enough blood cells).

Diagnosis of schwachman-diamond syndrome

The most accurate and precise method for the detection and diagnosis of Schwachman-Diamond Syndrome is gene testing and mutation detection in the SBDS gene.

Preventative measures for further complications

• Testing for genetic carriers of the disease.
• Prenatal diagnosis for pregnancies at risk.

Treatment of schwachman-diamond syndrome

Following SDS diagnosis, patients need to start pancreatic enzyme replacement therapy. It has been demonstrated that these patients respond well to such type of treatment.³ Additionally, levels of fat-soluble vitamins should be monitored frequently (every six to twelve months), and any abnormalities should be fixed accordingly. As the exocrine pancreatic function improves over time, it may be necessary to stop using enzyme replacement. Furthermore, patients ought to receive nutritional guidance from a licensed dietician in addition to routine growth monitoring by repeated weight and height assessments.

Platelets and packed red blood cell (PRBC) transfusions are the treatment options for anaemia and thrombocytopenia, respectively. Iron chelation should be initiated in patients who require frequent PRBC transfusions. Every three to four months, patients should have routine blood screening with a haematologist to check for leukaemia, myelodysplastic disease, or bone marrow failure.

Other diseases

SDS has symptoms that can be found in other diseases. Therefore, careful observations and diagnosis should be made considering different diagnostic methods. As the main signs and symptoms of SDS are exocrine pancreatic dysfunction and bone marrow failure, some of the conditions with similar characteristics are: 

Exocrine pancreatic dysfunction

• Cystic Fibrosis
• Johanson-Blizzard syndrome
• Pearson bone marrow pancreas syndrome

Bone marrow failure

• Diamond-Blackfan anaemia
• Fanconi anaemia
• Dyskeratosis congenita

Summary

Shwachman-Diamond Syndrome is an uncommon genetic condition that is the result of a mutation in the SBDS gene. Symptoms usually start presenting in early infancy (4-6 months). However, there are cases when symptoms may appear later in life, although it is unusual. Diagnosis can be made using genetic testing for the mutated gene and thorough clinical examination looking for certain abnormalities. There is no cure for SDS. Nevertheless, there are different treatment options depending on the signs and symptoms present. In most cases, upon correct diagnosis and treatment, individuals can lead relatively normal lives. 

FAQs

What is shwachman-diamond syndrome (SDS)?

A hereditary condition called Shwachman-Diamond Syndrome mostly affects the skeletal system, pancreas, and bone marrow. Neutrophil (a kind of white blood cell) deficiency, pancreatic insufficiency, and skeletal deformities are its key characteristics.

What is the likelihood of having SDS?

With an estimated prevalence of 1 in 76,000 people, SDS is regarded as a relatively uncommon disorder. Because it is not as well-known as some other hereditary disorders, specific knowledge is crucial.

What is the cause of SDS?

The main cause of SDS is mutations in the SBDS gene, which is found on chromosome 7. The distinctive symptoms of the disease are caused by these genetic abnormalities that interfere with regular cellular functions.

Is SDS treatable?

Although there is no cure for SDS, there are many treatment options, according to the signs and symptoms presented by the patient, that can improve the overall quality of life of the individual.