keratan-sulfate and Mucopolysaccharidosis-II

To explore the correlation between glycosaminoglycan (GAG) levels and mucopolysaccharidosis (MPS) type, we have evaluated the GAG levels in blood of MPS II, III, IVA, and IVB and urine of MPS IVA, IVB, and VI by tandem mass spectrometry. Dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS; mono-sulfated KS, di-sulfated KS), and the ratio of di-sulfated KS in total KS were measured. Patients with untreated MPS II had higher levels of DS and HS in blood while untreated MPS III had higher levels of HS in blood than age-matched controls. Untreated MPS IVA had higher levels of KS in blood and urine than age-matched controls. The ratio of blood di-sulfated KS/total KS in untreated MPS IVA was constant and higher than that in controls for children up to 10 years of age. The ratio of urine di-sulfated KS/total KS in untreated MPS IVA was also higher than that in age-matched controls, but the ratio in untreated MPS IVB was lower than controls. ERT reduced blood DS and HS in MPS II, and urine KS in MPS IVA patients, although GAGs levels remained higher than the observed in age-matched controls. ERT did not change blood KS levels in MPS IVA. MPS VI under ERT still had an elevation of urine DS level compared to age-matched controls. There was a positive correlation between blood and urine KS in untreated MPS IVA patients but not in MPS IVA patients treated with ERT. Blood and urine KS levels were secondarily elevated in MPS II and VI, respectively. Overall, measurement of GAG levels in blood and urine is useful for diagnosis of MPS, while urine KS is not a useful biomarker for monitoring therapeutic efficacy in MPS IVA.

Topics: Adolescent; Adult; Biomarkers; Child; Child, Preschool; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Keratan Sulfate; Male; Mucopolysaccharidoses; Mucopolysaccharidosis II; Mucopolysaccharidosis III; Mucopolysaccharidosis IV; Mucopolysaccharidosis VI; Tandem Mass Spectrometry; Young Adult

Acidic glycosaminoglycans (GAGs) and gangliosides were analyzed in the brains from control fetuses, fetal Hurler syndrome, control children and three patients affected by genetic mucopolysaccharidosis (Hurler, Hunter and Morquio syndromes). GAGs contents in the brains from patients with Hurler and Hunter syndromes were approximately 1.5-3.0-fold greater as compared with those controls, and most of the GAGs were much more degraded than those from controls. Dermatan sulfate (DS), which was not identified in the control brains, comprised about 20--40% of the total GAGs. On the other hand, GAGs content and molecular weight distribution in the brain from the patient affected by Morquio syndrome were similar to those in the control brains. GAGs content in the brain from fetal Hurler syndrome was also 2.0-fold greater and DS, which was not detected in the control fetal brains, comprised 1.6% of the total GAGs. However, the molecular weight distribution of the GAGs was similar to those of the control fetal brains. The total amount of the brain gangliosides in all patients assayed here was similar to those in the control brains. However, a greater amount of GM1- and Gm2-gangliosides was observed in the brains from patients with Hurler and Hunter syndromes.

Topics: Adolescent; Brain; Brain Chemistry; Child; Child, Preschool; Dermatan Sulfate; Fetus; Gangliosides; Glycosaminoglycans; Humans; Infant; Keratan Sulfate; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis IV