Shwachman-Diamond syndrome (SDS) is a rare condition treated at Great Ormond Street Hospital (GOSH) which affects the pancreas, bone marrow and skeleton. Only 200 or so people have been diagnosed with this condition worldwide. It affects all races and ethnic groups equally and is more common in males than females but more research is needed to understand why.
SDS was named after the two doctors (Dr Shwachman and Dr Diamond) who first described the condition in the 1960s.
What causes Shwachman-Diamond syndrome?
SDS is a genetic condition, caused by a mutation on a particular gene on Chromosome 7. In the majority of cases, this gene mutation is passed on from parent to child in an autosomal recessive manner. This means that each parent has to pass on the faulty gene for the child to have SDS. In around 10 per cent of cases, the gene mutation is not passed on but develops by chance. The specific gene mutation cannot be identified in some children, which implies that other gene mutations may cause SDS.
The gene mutation affects how the pancreas develops, stopping certain cells forming and replacing them with fatty tissue instead. The role of the pancreas is to release substances called enzymes, which break down food so that the nutrients it contains can be absorbed easily by the body. In SDS, these enzymes are not produced by the pancreas, so goodness cannot be absorbed from food as it should.
The faulty gene also stops the bone marrow producing blood cells effectively. Usually, the long bones in the body, such as the thighbone, are like factories producing new blood cells on a continuous basis. In SDS, the bone marrow does not make blood cells properly. In some children, only one type of blood cells is affected but other children may not develop blood cells at all – this is called aplastic anaemia. The lack of goodness absorbed from food also has an impact on bone development, as certain key vitamins and minerals are missing, leading to poor bone growth.
What are the signs and symptoms of Shwachman-Diamond syndrome?
The signs and symptoms of SDS can be grouped as follows:
As the pancreas does not release enzymes, food cannot be broken down and nutrients absorbed as they should be. This usually becomes obvious within a few days or weeks of birth, as growth and weight gain is lower than expected due to the lack of nutrients being taken in by the body. This may be referred to as ‘failure to thrive’. The lack of nutrients also shows in the faeces (poo) passed, which may be watery (diarrhoea) and greasy.
Blood and bone marrow symptoms
As the bone marrow does not produce new blood cells as it should, children may have low levels of the various types of blood cell circulating in their body.
If they have too few white blood cells, which fight off infection, they will be more at risk of catching an infection and it lasting longer or being more serious than in other children. This is called neutropenia.
If red blood cell production is affected, they may develop anaemia, causing tiredness and lack of energy.
If platelet production is reduced, they may bruise or bleed more easily than usual as platelets are responsible for blood clotting. Low platelet levels are referred to as thrombocytopenia.
Occasionally, production of all three types of blood cell is affected (pancytopenia).
Children with SDS also seem to be at a higher risk than other children of developing certain cancers of the blood and bone marrow, although this risk is still small.
Children with SDS have less dense bones than usual because the vitamins and minerals needed for strong bone growth are not being absorbed from food. This can increase the likelihood of bone fractures. The production of new bone – needed for growth and after injury – is also affected. Some children develop changes in the growth plates or curvature of the spine (scoliosis).
In addition to pancreas, blood and bone problems, children can have an inflamed gut (enteropathy), problems with their teeth (crowding, poor quality of enamel), mild inflammation of the liver (usually not significant) and in rare cases, problems with other organs such as the heart.
How is Shwachman-Diamond syndrome diagnosed?
SDS can be diagnosed using a variety of tests. Blood tests will measure the number of each type of blood cell present and can also show how the pancreas, liver and kidneys are working. Other blood tests may try to identify the gene mutation known to cause SDS. Stool samples will be taken for analysis as well.
The child will also need a bone marrow aspiration or biopsy, which is a short procedure under general anaesthetic to take a sample of bone marrow for examination in our laboratory. This will show whether thechild’s bone marrow is making blood cells as it should or whether certain types are not being produced.
If the child has skeletal problems, x-rays or other imaging scans may be suggested to diagnose these and monitor them as thechild grows older.
How is Shwachman-Diamond syndrome treated?
As SDS is such as rare disease affecting various body systems, treatment is best managed in a specialist centre with multi-disciplinary team involvement. The clinicians involved will vary for child to child but will usually include a gastroenterologist (specialist in digestive disorders), a dietitian (specialist in food and nutrition), a haematologist (blood specialist) and an orthopaedic surgeon (bone specialist) and at GOSH, a dentist.
The first aim of treatment is to manage the symptoms of SDS. This includes treatment for the pancreatic problems so that the child can absorb goodness from the food they eat, enabling more normal growth and development. This usually involves the child having enzyme replacement therapy – that is, tablets or powders containing manmade versions of enzymes to take with food so that it is broken down and nutrients absorbed. Around half of children will only need to have enzyme replacement therapy until school age as for some reason the pancreas starts to make enzymes at this point.
The problems with blood cells production will also be treated, sometimes with transfusions of blood or platelets or by giving a medicine that stimulates the bone marrow to produce more blood cells. Infections and high temperatures can be more difficult to manage if a child’s white blood cell count is low so short stays in hospital for intravenous antibiotics may be needed. Medicines may also be needed to supplement the child’s diet and increase bone density.
Some children develop more serious bone marrow problems, and require a bone marrow transplant. New bone marrow may be donated by a member of the family or an unrelated donor so there are numerous tests that need to be carried out – on the donor as well as the child – to make sure that the ‘match’ is good enough. Once a donor has been identified, the child will have strong medicines to kill off their own bone marrow so the body is ready to receive the donated bone marrow.
What about behaviour, learning and school for children with Shwachman-Diamond syndrome?
Research has been carried out at GOSH to understand more about behaviour, learning and school for children with SDS. Nearly 90 per cent of children diagnosed with SDS living in the UK were involved in this research so we have a much better understanding now than we did a few years ago.
For instance, we understand that children with SDS may struggle to behave in the classroom – paying attention, keeping still and getting on with other children may be more difficult. Overall, children with SDS have been found to have a lower IQ than other children their age. However, these IQ scores fall within a range so individual children may have IQ scores lower than the average or higher than the average.
At school, children with SDS may have difficulty with literacy – particularly spelling, reading, listening and reading comprehension – and numeracy. They may also have trouble concentrating and organising themselves (executive functioning). Friendships with other children might be difficult to start and maintain, which may be linked to lower self-esteem and confidence.
It can be helpful for schools to look at how a child with SDS is getting on in classroom and playtime groups, adjusting activities or groupings where needed to increase their confidence. Giving a child responsibility for something within the class may be helpful as well. There are also ways of improving executive functioning, such as displaying timetables in a visual way, teaching children to break a large task into smaller chunks and providing examples of finished tasks to work towards.
What happens next?
Bacterial infections such as flu and sore throats can be common but prompt diagnosis and treatment can reduce their effects. Immunisation against common childhood infections according to the national schedule can also reduce the risk of some bacterial infections.
Children with SDS will need lifelong monitoring on a regular basis, not only to assess their physical problems such as blood cell production and skeletal issues but also their social and psychological functioning. At GOSH, we will monitor children with SDS until the age of 16 when their care will be transferred to an adult hospital.
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