Severity Scoring Tool for nGD

Elin Haf Davies became involved in the Gaucher world when she was recruited to co-ordinate the Zavesca clinical trial for Type III at Great Ormond Street Hospital, London. She identified a need and looked to fill it.

During her work on the trial she noticed how hard it was to have an assessment measure that children could comply with, but which gave meaningful data. It was from this experience, and through gaining knowledge about clinical research while studying for her Masters degree that she decided to develop a new means of assessment that was specific for Type III Gaucher patients. This led to her current PhD studies where she is exploring the use of a Severity Scoring Tool (which she has developed in collaboration with European experts), gait analysis and brain MRI data. Her research is almost complete and will be written up for publication before the end of the year. Elin provides a brief report on her research -

In 2007 the European Task Force for Neuronopathic Gaucher Disease (nGD) published a review of 55 patients from four European countries; Germany, Poland, Sweden and the UK. As part of this work, a Severity Scoring Tool (SST) was developed in an attempt to provide physicians with a means of monitoring the neurological progress of patients in a uniform way. The SST is a simple way of attributing a score to disease severity based on 11 neurological manifestations commonly seen in nGD.

Through incorporating the views of experts worldwide, further work has been done to modify and validate the SST. In a bid to \'test\' the value of the modified SST (mSST) and to report on the progress of the patients initially assessed, a follow up review was arranged. This work was supported by the Gaucher Association in the UK by way of a travel grant to cover my costs to visit Germany and Poland.  Unfortunately it was not possible to arrange visits to Sweden at this time.

Thirty nine of the patients originally assessed were reassessed nearly four years later. By using the mSST it was possible to report on the disease status of the patients assessed. Overall there had been progress in neurological involvement which was made evident by the overall increase in the mSST score. This increase was generally small which is reflective of the slow progressing nature of neurological disease in most nGD cases.

The mSST was able to detect a difference when comparing disease status and rate of progression in various genotypes. It appears that patients who are L444P homozygous and those with a D409H and L444P combined genotype were much milder with a slower rate of progression than those with heterozygote genotypes.

The SST is currently included in the revised recommendations for the management of nGD. It is hoped that through continued and expanded use, the SST will offer an improved insight into neurological outcome of the disease in the enzyme replacement era, and ultimately offer a means of monitoring the value of any new emerging therapies that may become available in the future.

My heartfelt thanks go to the UK Gauchers Association, Dr Ashok Vellodi, Dr Eugene Mengel and Professor Anna Tylki-Szymanska for their generous support of this work.

Four year follow-up of chronic neuronopathic Gaucher dise ase in Europe – using a modified severity scoring tool Davies, E., Mengel, E.,Tylki-Szymanska.A, Kleinotiene,G.,Vellodi, A J Inherit Metab Dis. 2011 May 28 {Epub ahead of print}

Brain white matter abnormalities in paediatric Gaucher Type I and Type III patients using diffusion tensor imaging: Study of white-matter brain
Davies, EH. Mengel, E.Tylki-Symanska, A Vellodi, A (2011)
J Inherit Metab Dis.

Management of neuronopathic Gaucher disease: revised recommendations.
Vellodi A, Tylki-Szymanska A, Davies EH, Kolodny E, Bembi B, Collin-Histed T, Mengel E, Erikson A, Schiffmann R. (2009)
J Inherit Metab Dis. Oct;32(5):660-4. 2009 Aug 5.