Quantitation of urinary glycosaminoglycans using dimethylene blue as a screening technique for the diagnosis of mucopolysaccharidoses: an evaluation.

BACKGROUND: The mucopolysaccharidoses (MPSs) are a group of inherited disorders due to defects in lysosomal enzymes catalysing the breakdown of glycosaminoglycans (GAGs). Usually they are detected using techniques to separate the accumulating GAGs in urine. However more recently an improved dye-based method measuring total urine GAG concentrations has become available. We have evaluated this method in the context of its application as a general screening technique in a routine metabolic laboratory. METHOD: An automated method for the quantitation of urinary GAGs using dimethylene blue was developed on a Cobas Fara analyser and evaluated in terms of its specificity, sensitivity and value in the diagnosis of the MPSs. The test was applied to 6156 anonymized urine samples received for tests for inherited metabolic diseases and to 121 samples from 85 patients with a variety of proven MPSs. RESULTS: A substantial number of samples from unaffected individuals gave abnormal results while a significant number of samples from patients with MPSs gave results within normal limits. CONCLUSION: In the context of our laboratory, it was not appropriate for use as a screening technique when applied to all specimens received for metabolic tests or as a first-line screening test for samples where mucopolysaccharide analysis was requested. However it was retained and used in parallel with cellulose acetate electrophoresis to aid interpretation.

Tyrosinemia type I--diagnostic issues and prenatal diagnosis.

A fifteen-month-old boy, born to consanguineously married couple, presented with asymptomatic hepatomegaly. Investigations revealed mildly deranged liver functions, necroinflammatory changes and cirrhosis on liver biopsy, a markedly raised alpha feto protein and tyrosine levels in plasma and a generalized aminoaciduria. His diagnosis of hereditary tyrosinemia was established on findings of raised serum and urine succinylacetone and a deficient activity of fumaryl acetoacetate hydroxylase enzyme. Prenatal diagnosis of hereditary tyrosinemia was performed in a subsequent pregnancy in this family from India.