Natural history and clinical assessment of Taiwanese patients with mucopolysaccharidosis IVA

Lin, Hui-Chen; Chuang, Chih Kuang; Chen, Ming Ren; Chiu, Pao Chin; Ke, Yu; Niu, Dau Ming; Tsai, Fuu Jen; Hwu, Wuh‐Liang; Lin, Jainn-Jim

doi:10.1186/1750-1172-9-21

Cited by 31 publications

(45 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A single-centre retrospective study evaluated 50 MPS patients, finding only 1 MPS VI patient with glaucoma (Ashworth et al 2006). One of 24 patients with MPSIVA from Taiwan (7%) had glaucoma (Lin et al 2014). The estimated prevalence of glaucoma among patients with MPS in the current study is between 2.1% and 12.5%.…”

Section: Discussionmentioning

confidence: 62%

Assessment and diagnosis of suspected glaucoma in patients with mucopolysaccharidosis

Ashworth

Flaherty

Pitz

et al. 2015

Acta Ophthalmologica

View full text Add to dashboard Cite

ABSTRACT.Purpose: The mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders, characterized by the accumulation of glycosaminoglycans within multiple organ systems including the eye. This study aimed to determine the prevalence of glaucoma in patients with MPS, as well as the characteristics, diagnosis and management of patients with MPS and glaucoma. Methods: A multicentre retrospective case-note review was carried out by ophthalmologists from four tertiary referral centres to identify patients with MPS who had been treated for glaucoma. Clinical ophthalmological data were collected using standardized data collection forms. Results: Fourteen patients were identified (27 eyes) of 294 patients with MPS. The prevalence of glaucoma ranged from 2.1% to 12.5%. The median age at diagnosis of glaucoma was 8 years. Diagnostic evaluation of glaucoma was incomplete in many patients: intraocular pressure was documented in all eyes, but optic disc appearance was only assessed in 67%, central corneal thickness in 26%, visual fields in 19% and iridocorneal angle in 15%. Conclusions: Patients with MPS need regular assessment for possible glaucoma including during childhood. Multiple factors contribute to the challenges of assessment, diagnosis and monitoring of glaucoma in these patients.

show abstract

Section: Discussionmentioning

confidence: 62%

Assessment and diagnosis of suspected glaucoma in patients with mucopolysaccharidosis

Ashworth

Flaherty

Pitz

et al. 2015

Acta Ophthalmologica

View full text Add to dashboard Cite

show abstract

“…Results are expressed as the mean ± SD. ECG and echocardiographic examinations were performed and measurements were compared with normal data as previously described (Henry, Gardin, & Ware, ; Lin et al, ). For hearing assessment by pure‐tone audiometry, the degree of hearing loss was classified by the age‐independent World Health Organization (WHO) clinical guidelines (World Health Organization, ).…”

Section: Methodsmentioning

confidence: 99%

Mucopolysaccharidosis III in Taiwan: Natural history, clinical and molecular characteristics of 28 patients diagnosed during a 21‐year period

Lin

Chuang

Lee

et al. 2018

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) has a variable age of onset and variable rate of progression. However, information regarding the natural history of this disorder in Asian populations is limited. A retrospective analysis was carried out for 28 patients with MPS III (types IIIA [n = 3], IIIB [n = 23], and IIIC [n = 2]; 15 males and 13 females; median age, 8.2 years; age range, 2.7-26.5 years) seen in six medical centers in Taiwan from January 1996 through October 2017. The median age at confirmed diagnosis was 4.6 years. The most common initial symptom was speech delay (75%), followed by hirsutism (64%) and hyperactivity (54%). Both z scores for height and weight were negatively correlated with age (r = -.693 and -0.718, respectively; p < .01). The most prevalent clinical manifestations were speech delay (100%) and intellectual disability (100%), followed by hirsutism (93%), hyperactivity (79%), coarse facial features (68%), sleep disorders (61%), and hepatosplenomegaly (61%). Ten patients (36%) had epilepsy, and the median age at the first seizure was 11 years. Thirteen patients (46%) experienced at least one surgical procedure. At the time of the present study, 7 of the 28 patients had passed away at the median age of 13.0 years. Molecular studies showed an allelic heterogeneity without clear genotype and phenotype correlations. MPS IIIB is the most frequent subtype among MPS III in the Taiwanese population. An understanding of the natural history of MPS III may allow early diagnosis and timely management of the disease facilitating better treatment outcomes.

show abstract

“…MPS II is caused by a deficiency in iduronate-2-sulfatase activity (IDS gene; Hunter: OMIM#309900; EC 3.1.6.13), which is involved in the lysosomal degradation of heparan sulfate (HS) and dermatan sulfate (DS). There are two major clinical forms, including mild and severe forms based on age at onset and severity of clinical manifestations [1][2][3][4]. The heterogeneity of the syndrome is assumed to reflect different mutations at the IDS locus affecting the expression of the IDS protein (enzyme), stability, and catalyzation function.…”

Section: Introductionmentioning

confidence: 99%

Identification and Functional Characterization of IDS Gene Mutations Underlying Taiwanese Hunter Syndrome (Mucopolysaccharidosis Type II)

Lin

Chern

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Hunter syndrome (mucopolysaccharidosis II; MPS II) is caused by a defect of the iduronate-2-sulfatase (IDS) gene. Few studies have reported integrated mutation data of Taiwanese MPS II phenotypes. In this study, we summarized genotype and phenotype correlations of confirmed MPS II patients and asymptomatic MPS II infants in Taiwan. Regular polymerase chain reaction and DNA sequencing were used to identify genetic abnormalities of 191 cases, including 51 unrelated patients with confirmed MPS II and 140 asymptomatic infants. IDS activity was analyzed in individual novel IDS variants using in vitro expression studies. Nineteen novel mutations were identified, in which the percentages of IDS activity of the novel missense mutations c.and c.1403G>A were significantly decreased (p < 0.001), c.254C>T and c.1025A>G were moderately decreased (p < 0.01), and c.851C>T was slightly decreased (p < 0.05) comparing with normal enzyme activity. The activities of the other six missense mutations were reduced but were insignificant. The results of genomic studies and their phenotypes were highly correlated. A greater understanding of the positive correlations may help to prevent the irreversible manifestations of Hunter syndrome, particularly in infants suspected of having asymptomatic MPS II. In addition, urinary glycosaminoglycan assay is important to diagnose Hunter syndrome since gene mutations are not definitive (could be non-pathogenic).Sequencing data were obtained by scanning through the data to identify anomalies using Applied Biosystems Sequence Scanner Software v2.0 Sequence Trace Viewer and Editor (Applied Biosystems Co., CA, USA) and manual progressive alignment. A total of 51 mutations of the IDS gene from the 191 cases, including the confirmed patients (n = 51) and infants suspected of having MPS II (n = 140) that were identified. The suspected MPS II infants were classified into two groups: Those with either 1) "positive" uGAG biochemistry examinations, reduction in leukocyte IDS enzyme activity, and identified IDS variations (n = 7); or 2) "negative" uGAG biochemistry examinations, reduction in leukocyte IDS enzyme activity and identified IDS variations (n = 133). The 51 mutations of the IDS gene included 32 missense (62.7%), 3 nonsense (5.9%), 2 silent (3.9%), 6 splicing (11.8%), 4 small deletions (7.8%), 3 gross deletions (5.9%), and 1 complex inversion (2%) ( Table 1). Of these mutations, 35 were reported and verified as being pathogenic for MPS II with varying degrees of severity or non-pathogenic , and the other 16 were novel mutations (Figure 1), which needed to be verified according to individual IDS activity by using in vitro expression studies.

show abstract

Natural history and clinical assessment of Taiwanese patients with mucopolysaccharidosis IVA

Cited by 31 publications

References 27 publications

Assessment and diagnosis of suspected glaucoma in patients with mucopolysaccharidosis

Assessment and diagnosis of suspected glaucoma in patients with mucopolysaccharidosis

Mucopolysaccharidosis III in Taiwan: Natural history, clinical and molecular characteristics of 28 patients diagnosed during a 21‐year period

Identification and Functional Characterization of IDS Gene Mutations Underlying Taiwanese Hunter Syndrome (Mucopolysaccharidosis Type II)

Contact Info

Product

Resources

About