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Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease

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Abstract

Fabry disease is an X-linked disorder of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme α-galactosidase A. This leads to the progressive accumulation of glycosphingolipids in lysosomes of most visceral tissues and in body fluids. Following successful clinical trials in adults, two recombinant enzyme preparations of α-galactosidase have recently been licensed in Europe for the treatment of Fabry disease and treatment in children has commenced. We now report the clinical findings and the levels of globotriaosylceramide in plasma and urine in three boys who have been treated with enzyme replacement therapy (agalsidase beta, Fabrazyme), 1 mg/kg for 2 years. In one boy there was a rapid improvement in all the clinical and biochemical parameters measured. This has been maintained. In the other two boys, who are siblings, there was no measurable clinical improvement after 1 year and the levels of globotriaosylceramide in plasma and urine, although lower than before treatment, were still considerably elevated. There was no evidence of blocking or neutralising antibodies so the dose of enzyme was increased to 2 mg/kg at 74 weeks of therapy. At 2 years their pain scores had improved but this was not accompanied by any reduction in the plasma or urine globotriaosylceramide levels. Conclusion:measurement of globotriaosylceramide in plasma and urine may not be the most appropriate marker to monitor the progression of treatment by enzyme replacement therapy in all patients. Certainly the subjective clinical improvement in the two brothers in this report outweighed the objective biochemical findings.

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Abbreviations

CTH :

globotriasosylceramide

ERT :

enzyme replacement therapy

FA :

fatty acid

LCB :

sphingosine

MS/MS :

tandem mass spectrometry

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Acknowledgements

We thank the Genzyme Corporation and the Fabry Support Group UK for financial support and the staff of the Enzyme Laboratory at Great Ormond Street Hospital for their help with the samples. Mutational analysis was done in the Clinical Molecular Genetics Laboratory at Great Ormond Street Hospital. Research at the Institute of Child Health and Great Ormond Street Hospital NHS Trust benefits from research and development funding received from the National Health Service Executive.

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Authors and Affiliations

  1. Biochemistry,Endocrinology and Metabolism Unit, Institute of Child Health, University College London, 30 Guilford Street, WC1N 1EH, London , UK

    Kevin Mills, Peter Morris, Elisabeth Young & Bryan Winchester

  2. Metabolic Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, UK

    Ashok Vellodi

  3. Clinical Mass Spectrometry Group, Waters Corporation MS Technologies Centre, Manchester, UK

    Donald Cooper & Michael Morris

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  1. Kevin Mills
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  2. Ashok Vellodi
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  3. Peter Morris
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  4. Donald Cooper
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  5. Michael Morris
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  6. Elisabeth Young
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  7. Bryan Winchester
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Correspondence to Elisabeth Young.

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Mills, K., Vellodi, A., Morris, P. et al. Monitoring the clinical and biochemical response to enzyme replacement therapy in three children with Fabry disease. Eur J Pediatr 163, 595–603 (2004). https://doi.org/10.1007/s00431-004-1484-z

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  • DOI: https://doi.org/10.1007/s00431-004-1484-z

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