TY - JOUR
T1 - Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses
AU - Kubaski, Francyne
AU - Suzuki, Yasuyuki
AU - Orii, Kenji
AU - Giugliani, Roberto
AU - Church, Heather J.
AU - Mason, Robert W.
AU - Dũng, Vũ Chí
AU - Ngoc, Can Thi Bich
AU - Yamaguchi, Seiji
AU - Kobayashi, Hironori
AU - Girisha, Katta M.
AU - Fukao, Toshiyuki
AU - Orii, Tadao
AU - Tomatsu, Shunji
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Mucopolysaccharidoses (MPSs) and mucolipidoses (ML) are groups of lysosomal storage disorders in which lysosomal hydrolases are deficient leading to accumulation of undegraded glycosaminoglycans (GAGs), throughout the body, subsequently resulting in progressive damage to multiple tissues and organs. Assays using tandem mass spectrometry (MS/MS) have been established to measure GAGs in serum or plasma from MPS and ML patients, but few studies were performed to determine whether these assays are sufficiently robust to measure GAG levels in dried blood spots (DBS) of patients with MPS and ML. Material and methods In this study, we evaluated GAG levels in DBS samples from 124 MPS and ML patients (MPS I = 16; MPS II = 21; MPS III = 40; MPS IV = 32; MPS VI = 10; MPS VII = 1; ML = 4), and compared them with 115 age-matched controls. Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Subsequently, dermatan sulfate (DS), heparan sulfate (HS-0S, HS-NS), and keratan sulfate (mono-sulfated KS, di-sulfated KS, and ratio of di-sulfated KS in total KS) were measured by MS/MS. Results Untreated patients with MPS I, II, VI, and ML had higher levels of DS compared to control samples. Untreated patients with MPS I, II, III, VI, and ML had higher levels of HS-0S; and untreated patients with MPS II, III and VI and ML had higher levels of HS-NS. Levels of KS were age dependent, so although levels of both mono-sulfated KS and di-sulfated KS were generally higher in patients, particularly for MPS II and MPS IV, age group numbers were not sufficient to determine significance of such changes. However, the ratio of di-sulfated KS in total KS was significantly higher in all MPS patients younger than 5 years old, compared to age-matched controls. MPS I and VI patients treated with HSCT had normal levels of DS, and MPS I, VI, and VII treated with ERT or HSCT had normal levels of HS-0S and HS-NS, indicating that both treatments are effective in decreasing blood GAG levels. Conclusion Measurement of GAG levels in DBS is useful for diagnosis and potentially for monitoring the therapeutic efficacy in MPS.
AB - Mucopolysaccharidoses (MPSs) and mucolipidoses (ML) are groups of lysosomal storage disorders in which lysosomal hydrolases are deficient leading to accumulation of undegraded glycosaminoglycans (GAGs), throughout the body, subsequently resulting in progressive damage to multiple tissues and organs. Assays using tandem mass spectrometry (MS/MS) have been established to measure GAGs in serum or plasma from MPS and ML patients, but few studies were performed to determine whether these assays are sufficiently robust to measure GAG levels in dried blood spots (DBS) of patients with MPS and ML. Material and methods In this study, we evaluated GAG levels in DBS samples from 124 MPS and ML patients (MPS I = 16; MPS II = 21; MPS III = 40; MPS IV = 32; MPS VI = 10; MPS VII = 1; ML = 4), and compared them with 115 age-matched controls. Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Subsequently, dermatan sulfate (DS), heparan sulfate (HS-0S, HS-NS), and keratan sulfate (mono-sulfated KS, di-sulfated KS, and ratio of di-sulfated KS in total KS) were measured by MS/MS. Results Untreated patients with MPS I, II, VI, and ML had higher levels of DS compared to control samples. Untreated patients with MPS I, II, III, VI, and ML had higher levels of HS-0S; and untreated patients with MPS II, III and VI and ML had higher levels of HS-NS. Levels of KS were age dependent, so although levels of both mono-sulfated KS and di-sulfated KS were generally higher in patients, particularly for MPS II and MPS IV, age group numbers were not sufficient to determine significance of such changes. However, the ratio of di-sulfated KS in total KS was significantly higher in all MPS patients younger than 5 years old, compared to age-matched controls. MPS I and VI patients treated with HSCT had normal levels of DS, and MPS I, VI, and VII treated with ERT or HSCT had normal levels of HS-0S and HS-NS, indicating that both treatments are effective in decreasing blood GAG levels. Conclusion Measurement of GAG levels in DBS is useful for diagnosis and potentially for monitoring the therapeutic efficacy in MPS.
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U2 - 10.1016/j.ymgme.2016.12.010
DO - 10.1016/j.ymgme.2016.12.010
M3 - Article
C2 - 28065440
AN - SCOPUS:85008490381
SN - 1096-7192
VL - 120
SP - 247
EP - 254
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 3
ER -
