1232 BETA-GLUCURONIDASE DEFICIENCY: A MUCOPOLYSACCHARIDOSIS WITH CHONDROITIN SULFATURIA

Abstract

Beta-glucuronidase deficiency is an autosomal recessive mucopolysaccharidosis with variable clinical manifestations similar to the other mucopolysaccharidoses. The urinary excretion of acid mucopolysaccharides (AMPS) has not been very clear, with reports suggesting the excretion of dermatan, heparan and chondroitin sulfates. These suggestions were based primarily on electrophoretic mobility. This report deals with the isolation and characterization of the urinary AMPS from three unrelated patients with β-glucuronidase deficiency. Urinary AMPS were isolated using gel chromatography with Sephadex G-25, followed by precipitation of the AMPS fraction with cetylpiridinium chloride. Dermatan sulfate was identified by the formation of a complex with CuSO4, the elution pattern from Dowex 1, X2Cl− and susceptibility to chondroitinases. Heparan sulfate was estimated by the determination of the N-sulfated hexosamine, a reaction specific for this compound. Chondroitin 4 and 6 sulfates were determined by the pattern of elution from Dowex 1 and digestibility with chondroitinase AC. Total AMPS isolated ranged from 18.4mg to 71.0mg/24h. The major fraction (>90%) was chondroitin 4/6 sulfate. Dermatan sulfate comprised <8% and heparan sulfate <2%. Gas chromatography/mass spectrometry of the uronic acids hydrolyzed from these fractions confirmed these findings. These studies indicate that chondroitin sulfaturia is a characteristic urinary finding of β-glucuronidase deficiency.