Although many of the issues described cover all types of Gaucher disease, patients with neuronopathic Gaucher disease (Types 2 and 3 Gaucher disease) have additional challenges associated with the neurological aspects of the disease.
In 2004, the European Commission licensed enzyme replacement therapy for the treatment of Type 3 Gaucher disease although prior to the license, patients were already receiving enzyme therapy off-label due to the dramatic improvement of their visceral disease. Although enzyme replacement therapy has improved the life expectancy and quality of life for many patients, there is no evidence that it crosses the blood brain barrier and the neurological aspects of this disease are being increasingly seen. Therefore, the challenge to develop a treatment that crosses the blood brain barrier still remains.
The neurological aspects of the disease remain challenging for patients and their families and present an unknown future regarding quality of life, life expectancy, ability to function in society and the impact on education.
Many patients with type 3 Gaucher disease receive enzyme replacement therapy in high doses and one infusion can take many hours. Increasingly a small portable device called an Intermate (manufactured by Baxter) is being used that has the advantage that it operates without electricity, and has no moving parts. It has enabled patients to move around freely and go out whilst receiving their treatment.
In 2003, a clinical trial of substrate reduction therapy with Miglustat (Zavesca) in Type 3 Gaucher disease began at two sites, one in the UK and the other in the US, involving thirty patients. It is hoped that this drug will cross the blood brain barrier and slow down neurological progression, however the clinical trial has proven to be a stressful time for many patients and their families. The drug must be taken orally up to three times a day and is delivered in a capsule that must be swallowed. This has been a challenge for many of the young children who have had difficulties in swallowing the capsules. The results of the trial are expected in late 2005.
Formation of a support service for neuronopathic Gaucher disease families in the UK Gaucher disease is rare and Types 2 and 3 Gaucher disease are even rarer. Most patient groups worldwide know of very few patients with Type 2 and 3 and when patients are newly diagnosed, usually in their first year of life, it can be difficult for families to meet other families to exchange and provide emotional and practical support.
In 1997, the UK Gauchers Association recruited Tanya Collin-Histed, whose daughter was diagnosed with Type 3 Gaucher disease at 16 months old, to join their Executive Committee to focus on raising awareness of the neurological form of the disease and to support families, whereas previously, the group’s attention had mainly focused on Type 1. This enabled the group to offer Type 3, and in some cases Type 2 families someone who understood the issues they faced. Together with Dr Ashok Vellodi from Great Ormond Street Hospital in London, she set out to raise the profile and understanding of neuronopathic Gaucher disease and bring families together to support each other.
Discovering that a child has neuronopathic Gaucher disease is devastating but to learn that there are few other sufferers, that there is little information available or known about the disease, and that there is not an effective treatment for the neurological aspects of the disease is at first incomprehensible. The provision of emotional and practical support in this situation is essential and this has included visiting new families in their homes and in hospital to provide emotional support and practical information. Often just by meeting an older child with the disease helps families to be more positive about the future.
In 1998 at the 3rd European Working Group for Gaucher Disease, the UK patient representative for neuronopathic Gaucher disease made a plea to develop a consensus paper for Europe on the management of Neuronopathic Gaucher disease as treatment varied considerably in different countries in terms of dosage of enzyme replacement therapy and clinical management. The European Working Group took forward the request and a Taskforce led by Dr Vellodi was formed. Clinicians from the UK, Sweden, Italy, Germany and Poland together with the UK neuronopathic patients’ representative met in the UK and developed a European Paper on the ‘Management of Neuronopathic Gaucher Disease’. The Consensus paper was published in ‘The Journal of Inherited Metabolic Diseases’ in 2001and will be reviewed at regular intervals.
Neuronopathic Gaucher Disease Booklets
Little or no information was available for families and non-medical professionals (such as teachers) involved in the day-to-day care of these patients. Consequently, in 2001, two booklets were written by Tanya Collin-Histed and Dr Ashok Vellodi entitled ‘Neuronopathic Gaucher Disease: A Guide for Parents’ and ‘Neuronopathic Gaucher Disease: Special Educational Needs’. Both booklets were produced by Great Ormond Street Hospital Trust and posted onto its website. The booklets were distributed to all known families in the UK and sent to other European patient groups for information and the Italian Gaucher Association translated the booklets into Italian for their own families. The booklets were re-written and updated in 2004 by the authors.
Neuronopathic Family Conferences
Bringing families together has always been a priority and an important aspect of support. In 1997, Dr Vellodi held a Fun Day in London for all the families attending Great Ormond Street Hospital that included activities for the children and talks for the families. This successful event highlighted the value to families of getting together to share their experiences and listen to talks about the disease and for many families, this was the first time they had met other families. In 1998, the UK Gaucher Association held separate sessions for Type 3 families at their annual conference in London and in 1999, the first Type 3 Family Conference was held in Northampton, UK. A dozen UK families attended the conference and a programme for the children was provided so that the parents could listen to presentation on topics such as eye movements, substrate reduction therapy, special educational needs and the auditory pathway.
In 2004, a European Family Conference was held in the UK that was attended by families from the UK, Sweden, Italy, New Zealand, Serbia and Montenegro, Jordan and Germany. Many of the families from outside the UK had never met another family with a child with Type 3 Gaucher disease and the event highlighted the need for patient groups throughout Europe and further away to meet regularly. The European Gaucher Alliance has an important role to play in this.
Families coping with Neuronopathic Gaucher Disease
The stress of the disease on the patient and their families can be enormous and have devastating effects. Marriages can break down and parents may have to give up work or work part-time which affect income levels. The regular trips to hospital for check-ups or reoccurring illnesses means time off work or school that may cause additional problems.
The uncertainty regarding the long term neurological outcome and the lack of a really effective treatment are difficult to deal with. Society’s understanding of the condition is also limited and therefore for patients and their families coping with everyday life can be a real challenge. These areas include education, employment and independence.
All patients have an eye movement problem horizontally and in some cases vertically, and in addition, the majority have some auditory processing problems and other cognitive issues. The patients look normal, are not blind or deaf and therefore present a real challenge to schools and colleges and the majority will need some degree of support to access the school curriculum.
Unfortunately, they do not fit neatly into the ‘boxes’ designed by educational authorities for providing support and there is a lack of understanding of their needs. Parents of other children with Type 3 Gaucher disease who have been through this process can be a tremendous support and the two booklets mentioned above offer practical information on how to get the support your child needs. As more is understood, hopefully the support available to the patients as they grow up and become adults will improve and enable them to access employment and live independently to some degree.
The UK Gauchers Association are delighted to announce that the fund has now been expanded to provide support in other areas of education. Find out more here