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Editor—Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of the enzymes catalysing the stepwise degradation of glycosaminoglycans (GAG). Bone marrow transplantation can slow down or reverse some of the features of these diseases. Enzyme replacement (ERT) studies in several animal models of MPS disorders have shown promising results1-3; human clinical trials of ERT in MPS type I have only recently become possible.4 The clinical symptoms of MPS usually become evident only between the second and third years of life. This therefore argues for early therapeutic intervention before the development of irreversible changes.
Quantitative measurement of urinary GAG (glycosaminoglycans) can be used to diagnose MPS. We investigated the change in urinary excretion of GAG to use for early diagnosis.
Random urine samples were obtained from 570 neonates on days 2–6 of life. The samples were obtained from 320 boys and 250 girls with birthweights of mean 3137 (SD 374) g and gestational ages of 39.7 (1.1) weeks. Urine specimens were collected from 85 neonates on day 2; 254 on day 3; 92 on day 4; 65 on day 5; and 74 on day 6. The babies had been born after an uneventful pregnancy and delivery and were not known to have any specific clinical abnormalities. Urine samples were also obtained from 1328 infants aged between 1 and 12 months old who had no symptoms of MPS, and from five MPS patients aged 1 month or less (MPS type II, 15 days old, 978 mg GAG/g creatine; MPS type II, 26 days old, 940 mg GAG/g creatine; MPS type II 1 month old, 1177 mg GAG/g creatine; MPS type III, 1 month old, 1180 mg GAG/g creatine; MPS VII, 1 month old), 205 mg GAG/g creatine.
The urine collector (ATOM pediatric urine collector, ATOM medical Co, Japan) was removed as soon as it was full of urine; it was then immediately stored at −20°C until analysis. After thawing at room temperature the urine were analysed as follows. Urinary excretion of GAG was measured using the DMB method5 and the urinary creatinine concentration was measured using the Jaffe method.6 Both measurements were performed using an MR 5000 plate reader (Dynatech, USA). The Wilcoxon rank sum test for unpaired data was used to compare groups.
Figure 1 shows the urinary GAG:creatinine ratio for normal neonates and infants and for five MPS patients. Urinary excretion of GAG decreased each day after birth until day 5 of life. The median for the GAG:creatinine ratio was 459.0, 446.4, 400.0, 323.0, and 311.5 mg/g on days 2, 3, 4, 5 and 6, respectively. Between days 2 and day 4 of life, the decrease was significant. Urinary excretion of GAG in the normal neonates was much lower than in the five MPS patients: type II, 15 days of age, 978 mg GAG/g creatinine; type II, 26 days old, 940 mg GAG/g creatinine; type II, 1 month old, 1177 mg GAG/g creatinine; type III, 1 month old, 1180 mg GAG/g creatinine; type VII, 1 month old 1205 mg GAG/g creatinine.
The GAG:creatinine ratio in MPS patients was much higher than in normal infants. We conclude that these results might be useful for the early diagnosis of MPS.