Biomarkers in patients with mucopolysaccharidosis type II and IV

Fujitsuka, Hideki; Sawamoto, Kazuki; Peracha, Hira; Mason, Robert W.; Mackenzie, William G.; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Kenji E.; Orii, Tadao; Fukao, Toshiyuki; Tomatsu, Shunji

doi:10.1016/j.ymgmr.2019.100455

Cited by 43 publications

(50 citation statements)

References 54 publications

(74 reference statements)

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“…However, controlled clinical studies should be conducted. A study performed by Kubaski et al [9] has demonstrated that HSCT improves ADL scores, MRI findings, cognitive function, and reduction of blood GAG levels in severe MPS II patients [9][10][11][12][13][14][15][16]19,28]. There was little improvement in HSCT treated attenuated MPS II patients.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation

et al. 2020

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The effectiveness of hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis type II (MPS II, Hunter disease) remains controversial although recent studies have shown HSCT provides more clinical impact. This study aims to evaluate the long-term effectiveness of HSCT using the activity of daily living (ADL) scores in patients with MPS II. Sixty-nine severely affected MPS II patients (19 patients who received HSCT and 50 untreated patients) and 40 attenuated affected patients (five with HSCT and 35 untreated) were investigated by a simplified ADL questionnaire. The frequency of clinical findings and the scores of ADL (verbal, gross motor, and the level of care) were analyzed statistically. The mean age of onset of 19 severely affected patients who received HSCT was 1.40 years ± 1.06, which is not statistically different from that of 50 untreated patients (p = 0.11). Macroglossia, frequent airway infection, hepatosplenomegaly, joint contracture, and sleep apnea were less frequent in the HSCT-treated group of severe MPS II patients. The severe phenotype HSCT treated group reported a statistically significant higher score of verbal function and gross motor function between the ages of 10 and 15 years and a higher level of care score between 10 and 20 years. Patients with the attenuated phenotype showed high ADL scores, and all of five HSCT treated patients reported a lower frequency of frequent airway infection, coarse skin, umbilical/inguinal hernia, hepatosplenomegaly, heart valve disorders, and carpal tunnel. In conclusion, HSCT is effective, resulting in improvements in clinical features and ADL in patients with MPS II. HSCT should be re-reviewed as a therapeutic option for MPS II patients.

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Section: Discussionmentioning

confidence: 99%

Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation

et al. 2020

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“…Their decrease is dramatic in the first 6-12 months of treatment and is sustained over the years tending to normalize in almost all patients [29,[34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52]. However, blood and urine dermatan sulfate (DS) and heparan sulfate (HS) derived disaccharides, that are considered more suitable biomarkers for MPS I and II [120][121][122], were persistently elevated in long term ERT-treated MPS I and MPS II patients, and blood mono-and di-sulfated keratan sulfate were elevated in MPS IVA patients on ERT [122,123].…”

Section: Gags and Other Possible Biomarkersmentioning

confidence: 99%

“…It has been suggested that pro-inflammatory factors can be used as biomarkers for monitoring the efficacy of ERT. For this reason, anti-inflammatory/anti-oxidant drugs are proposed as an additive treatment to ERT [57,122].…”

Section: Gags and Other Possible Biomarkersmentioning

confidence: 99%

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Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

Parini

Deodato

2020

IJMS

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The aim of this review is to summarize the evidence on efficacy, effectiveness and safety of intravenous enzyme replacement therapy (ERT) available for mucopolysaccharidoses (MPSs) I, II, IVA, VI and VII, gained in phase III clinical trials and in observational post-approval studies. Post-marketing data are sometimes conflicting or controversial, possibly depending on disease severity, differently involved organs, age at starting treatment, and development of anti-drug antibodies (ADAs). There is general agreement that ERT is effective in reducing urinary glycosaminoglycans and liver and spleen volume, while heart and joints outcomes are variable in different studies. Effectiveness on cardiac valves, trachea and bronchi, hearing and eyes is definitely poor, probably due to limited penetration in the specific tissues. ERT does not cross the blood–brain barrier, with the consequence that the central nervous system is not cured by intravenously injected ERT. All patients develop ADAs but their role in ERT tolerance and effectiveness has not been well defined yet. Lack of reliable biomarkers contributes to the uncertainties about effectiveness. The data obtained from affected siblings strongly indicates the need of neonatal screening for treatable MPSs. Currently, other treatments are under evaluation and will surely help improve the prognosis of MPS patients.

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“…Although serum, liver and brain had a similar ratio of HS:DS, which was lower than that seen in the urine and kidney, a distribution of oligosaccharides which ranked from most to least abundant between serum, liver and brain was observed, suggesting that serum more closely reflects the oligosaccharides of the brain and liver and may therefore be a more informative measurement of disease burden than urine [59]. In addition, Kahn et al [47] and Fujitsuka et al [60] also stated that blood KS remained high while uKS was reduced during ERT. The fact of the lack of a reduction of blood KS should be notable because this is critical evidence that uKS is ineffective as a biomarker to prove therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 93%

An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan

Lin

Lee

et al. 2019

Diagnostics

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Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.

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Biomarkers in patients with mucopolysaccharidosis type II and IV

Cited by 43 publications

References 54 publications

Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation

Assessment of Activity of Daily Life in Mucopolysaccharidosis Type II Patients with Hematopoietic Stem Cell Transplantation

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan

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