Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses

Francyne Kubaski, Yasuyuki Suzuki, Kenji Orii, Roberto Giugliani, Heather J. Church, Robert W. Mason, Vũ Chí Dũng, Can Thi Bich Ngoc, Seiji Yamaguchi, Hironori Kobayashi, Katta M. Girisha, Toshiyuki Fukao, Tadao Orii, Shunji Tomatsu

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalMolecular Genetics and Metabolism
Volume120
Issue number3
DOIs
Publication statusPublished - 01-03-2017

Fingerprint

Mucolipidoses
Mucopolysaccharidoses
Glycosaminoglycans
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Blood
Mucopolysaccharidosis VI
Dermatan Sulfate
Mucopolysaccharidosis VII
Mucopolysaccharidosis III
Mucopolysaccharidosis IV
heparitinsulfate lyase
Assays
Keratan Sulfate
Heparitin Sulfate
Disaccharides
Hydrolases
Mass spectrometry
Polymers
Tandem Mass Spectrometry

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Kubaski, F., Suzuki, Y., Orii, K., Giugliani, R., Church, H. J., Mason, R. W., ... Tomatsu, S. (2017). Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses. Molecular Genetics and Metabolism, 120(3), 247-254. https://doi.org/10.1016/j.ymgme.2016.12.010
Kubaski, Francyne ; Suzuki, Yasuyuki ; Orii, Kenji ; Giugliani, Roberto ; Church, Heather J. ; Mason, Robert W. ; Dũng, Vũ Chí ; Ngoc, Can Thi Bich ; Yamaguchi, Seiji ; Kobayashi, Hironori ; Girisha, Katta M. ; Fukao, Toshiyuki ; Orii, Tadao ; Tomatsu, Shunji. / Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses. In: Molecular Genetics and Metabolism. 2017 ; Vol. 120, No. 3. pp. 247-254.
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title = "Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses",
abstract = "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.",
author = "Francyne Kubaski and Yasuyuki Suzuki and Kenji Orii and Roberto Giugliani and Church, {Heather J.} and Mason, {Robert W.} and Dũng, {Vũ Ch{\'i}} and Ngoc, {Can Thi Bich} and Seiji Yamaguchi and Hironori Kobayashi and Girisha, {Katta M.} and Toshiyuki Fukao and Tadao Orii and Shunji Tomatsu",
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Kubaski, F, Suzuki, Y, Orii, K, Giugliani, R, Church, HJ, Mason, RW, Dũng, VC, Ngoc, CTB, Yamaguchi, S, Kobayashi, H, Girisha, KM, Fukao, T, Orii, T & Tomatsu, S 2017, 'Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses', Molecular Genetics and Metabolism, vol. 120, no. 3, pp. 247-254. https://doi.org/10.1016/j.ymgme.2016.12.010

Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses. / Kubaski, Francyne; Suzuki, Yasuyuki; Orii, Kenji; Giugliani, Roberto; Church, Heather J.; Mason, Robert W.; Dũng, Vũ Chí; Ngoc, Can Thi Bich; Yamaguchi, Seiji; Kobayashi, Hironori; Girisha, Katta M.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji.

In: Molecular Genetics and Metabolism, Vol. 120, No. 3, 01.03.2017, p. 247-254.

Research output: Contribution to journalArticle

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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