Children with Gauchers Disease


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Dr Ashok Vellodi,who runs the paediatric Gauchers Centre at Great Ormond Hospital for Children, spoke about children with Gauchers disease at the 5th Conference.


Dr Vellodi began his talk by stressing that all children should start treatment on a high dose of 60 units per kilogram of body weight every two weeks and that children with Type 3 should receive a dose of 120 units per kilogram every two weeks. He also emphasised that children should be monitored regularly. He said that his Centre and that of Dr Ed Wraith at the Royal Manchester Children's Hospital worked closely together and within common guidelines.

'Seventeen percent of individuals with Gauchers disease listed in the International Gaucher Collaborative Registry (IGCR) are children under the age of 18 years and the Registry holds details of 2,530 patients: currently 1,982 are adults and 511 are children. 98% of the adults are Type 1 and 2% are Type 3. Of the children, 79% are Type 1, 18% are Type 3 and 3% are Type 2.'

During his work at Great Ormond Street Hospital, Dr Vellodi said that he sees all children who suffer from a lysosomal disease of whom 10% have Gauchers disease. However 25% of the children seen as outpatients have Gauchers disease and two-thirds of the inpatients who suffer from a lyso-somal disorder have symptoms related to Gauchers disease. This is a result of the disease being treatable and it has become a paradigm or example of the impact of enzyme replacement therapy on clinical activity.

If a child with Gauchers disease presents with severe symptoms, a doctor must think of the possibility that the child could have neuronopathic disease. Even if these symptoms are not apparent immediately, they may develop later.

Family History

A child's family history including whether a sister or brother also has Gauchers disease must be taken and mutational analysis sought to discover a genotype-phenotype pattern (mutation-symptom correlation).

Childhood onset disease tends to be more severe. For example, 47% of the children reviewed at the NYU Medical Centre in New York had the N370S/84GG genotype (known to be associated with more severe disease) whilst only 14% of adults had it. Conversely only 18% of children had the N370S/N370S combination whilst 57% of adults had it. This confirms that the combination of N370S/N370S usually predicts a milder form of the disease. Only 3% of the children had the L444P/L444P combination (which is usually considered to cause neurological problems) but no adults had these mutations.

Splenectomy

Referring to whether patients had had their spleens removed, the statistics showed that out of 394 children, 93% still had a spleen, 6% had had a partial splenectomy and 0.6% a total splenec-tomy. In adults, 68% still had their spleens, 3% had a partial splenectomy and 29% had had a total splenectomy. Therefore while splenectomy is not as common in children as in adults, it remains nevertheless a problem.

Dr Vellodi stressed that it is important to avoid a total splenectomy in a child under the age of 5 years old as there is a severe risk of infection. In addition, a total splenectomy results in acceleration of neurological symptoms in patients with neuronopathic disease. A partial splenectomy can be totally bloodless but it is a potentially more risky operation than a total one if it is not carried out correctly.

After a splenectomy prevention of infections is paramount. This includes giving regular antibiotics, a HIB vaccination and a Pneumovax injection. There is now a new version of Pneumovax available which is thought to be better than the previous one where the response was poor. However research is still continuing into this as the new vaccine only covers seven strains of pneumococcus (forms of bacteria) and not 23 strains like the old version but the new Pneumovax may be more suitable for children under the age of two years.

Hip Replacements andFractures

Again quoting from the IGCR, Dr Vellodi said that out of 538 children under the age of 10, none of the children had had a hip replacement but 17 had evidence of avascular necrosis (death of the bone) of the hip joint and five had suffered a fracture in the femur (hip). Of 565 children up to the age of 18 years old, 14 had had a hip replacement, 19 had suffered avascular necrosis and 5 had had a fracture of the femur or hip.

Bone in Healthy Children

Dr Vellodi said there were two types of bone in all humans. Trabecular bone (which is spongy and metabolically more active) makes up 20% and cortical (compact) bone which makes up the other 80%. There is also bone marrow and fat.

Certain cells called osteoclasts break down bone and others called osteoblasts build up bone. In children, the rate of bone formation is greater than its destruction but in adults this is reversed. In addition, bone growth occurs at the end of bones and this is associated with the deposition of calcium. Thus the need for calcium and Vitamin D is higher in children. Normal adults should take 200 units of Vitamin D a day and adolescents should take 800 units a day.

Bone mass peaks at different ages in different sites. However for the lumber spine and femur (hip), this is usually at the age of 18 years with the maximum amount of growth (40-60%) achieved during puberty.

It is therefore important to improve peak bone mass as much as is possible. Of the factors responsible for peak bone mass, 80% are genetic and 20% environmental.

The activity of bone growth may be measured by DEXA (dual energy Xray absorptiometry) or by QCT (Quanti-tative CT Scanning). DEXA measures a specific area, looking at the whole bone as it cannot look at the trabecular and cortical bone separately.

Quantitative CT separates the trabecular from the cortical bone but at a relatively high radiation dose. A new QCT is being developed that uses less radiation.

Exercise

Dr Vellodi said that children with Gauchers disease should undertake careful exercise and have a structured programme of physiotherapy.

It is important to take weight-bearing exercise such as walking. Swimming is a good general exercise but does not increase bone mass as it is not weight bearing.

Dr Vellodi and Dr Wraith see children with all types of Gauchers disease.


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Source: Gauchers News March 2002.
© Copyright Gauchers Association 2002