Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients.

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Glycosaminoglycans (GAGs) are measured in urine to screen for mucopolysaccharidoses. Other assay procedures are only qualitative (spot tests), can give false-negative results (spot tests, turbidity tests), or are relatively laborious (uronic acid-carbazole test). The present spectrophotometric procedure, based on the color reaction with dimethylmethylene blue (DMB), can be performed directly on untimed urine samples without prior precipitation. Reference values were age dependent. We tested urines of 27 patients with various mucopolysaccharidoses and compared results by three other procedures (cetylpyridinium chloride turbidity tests at pH 4.8 and at pH 7.0, and the uronic acid-carbazole test). In the DMB assay, GAGs were increased in 26 of the 27 patients. The exception was a Morquio A patient, whose activity of the defective enzyme was higher than in classical Morquio patients. Uronic acid, measured in precipitated GAG by the carbazole test, was increased in 23 of the 25 patients so tested. In the turbidity test at pH 7.0, values were increased in 24 of the 27 patients. In contrast, with the citrate-buffered (pH 4.8) turbidity measurement, GAG content was increased in only 19 of the 27 patients. This rapid and easy DMB method is a reliable screening procedure for mucopolysaccharidoses and compares well with procedures used hitherto.