scholarly journals Aortic Root Dilatation in Taiwanese Patients with Mucopolysaccharidoses and the Long-Term Effects of Enzyme Replacement Therapy

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Hsiang-Yu Lin ◽  
Ming-Ren Chen ◽  
Chung-Lin Lee ◽  
Shan-Miao Lin ◽  
Chung-Lieh Hung ◽  
...  
Keyword(s):  
Aortic Root ◽  
Root Diameter ◽  
Z Score ◽  
Long Term Effects ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Mps Vi ◽  
Aortic Root Dilatation ◽  
Mps I ◽  
Mps Iii

Background: Cardiovascular abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular regurgitation and stenosis and cardiac hypertrophy. Only a few studies have focused on aortic root dilatation and the long-term effects of enzyme replacement therapy (ERT) in these patients. Methods: We reviewed echocardiograms of 125 Taiwanese MPS patients (age range, 0.1 to 19.1 years; 11 with MPS I, 49 with MPS II, 25 with MPS III, 29 with MPS IVA, and 11 with MPS VI). The aortic root diameter was measured at the sinus of Valsalva. Results: Aortic root dilatation (z score >2) was observed in 47% of the MPS patients, including 66% of MPS IV, 51% of MPS II, 45% of MPS VI, 28% of MPS III, and 27% of MPS I patients. The mean aortic root diameter z score was 2.14 (n = 125). The patients with MPS IV had the most severe aortic root dilatation with a mean aortic root diameter z score of 3.03, followed by MPS II (2.12), MPS VI (2.06), MPS III (1.68), and MPS I (1.03). The aortic root diameter z score was positively correlated with increasing age (n = 125, p < 0.01). For the patients with MPS II, III, and IV, aortic root diameter z score was also positively correlated with increasing age (p < 0.01). For 16 patients who had received ERT and had follow-up echocardiographic data (range 2.0–16.2 years), the mean aortic root diameter z score change was −0.46 compared to baseline (baseline 2.49 versus follow-up 2.03, p = 0.490). Conclusions: Aortic root dilatation was common in the patients with all types of MPS, with the most severe aortic root dilatation observed in those with MPS IV. The severity of aortic root dilatation worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS appears to stabilize the progression of aortic root dilatation.

scholarly journals Cardiac Evaluation Using Two-Dimensional Speckle-Tracking Echocardiography and Conventional Echocardiography in Taiwanese Patients with Mucopolysaccharidoses

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 62 ◽  
Author(s):  
Hsiang-Yu Lin ◽  
Chih-Kuang Chuang ◽  
Chung-Lin Lee ◽  
Ming-Ren Chen ◽  
Kuo-Tzu Sung ◽  
...  
Keyword(s):  
Speckle Tracking ◽  
Speckle Tracking Echocardiography ◽  
Left Ventricular ◽  
Z Score ◽  
Mps Ii ◽  
Mps Vi ◽  
Z Scores ◽  
Mps I ◽  
Mps Iii ◽  
Conventional Echocardiography

Background: Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders that can damage various organs, including the heart. Cardiac abnormalities have been observed in patients with all MPS types, with the most documented abnormalities being cardiac valvular regurgitation and stenosis, valvular thickening, and hypertrophic cardiomyopathy. Methods: Cardiac features of 53 Taiwanese patients with MPS (31 men and 22 women; age range 1.1–34.9 years; seven with MPS I, 16 with MPS II, nine with MPS III, 14 with MPS IVA, and seven with MPS VI) were evaluated using two-dimensional speckle-tracking echocardiography and conventional echocardiography. Results: The mean z scores of the global longitudinal strain (GLS), left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter of the 53 patients with MPS were 1.71, 0.35, 1.66, 1.03, and 3.15, respectively. Furthermore, z scores >2 were identified in 45%, 13%, 40%, 13%, and 70% of the GLS, LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most severe GLS was observed in those with MPS VI, followed by in those with MPS II and MPS I. The GLS z score was positively correlated with the LVMI z score (p < 0.01). Moreover, diastolic dysfunction (reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio < 1)) was identified in 12 patients (23%). Ejection and shortening fractions were abnormal in four (8%) and seven (13%) patients, respectively. Mitral regurgitation (MR) (92%) was the most common valvular heart disease, followed by aortic regurgitation (AR) (57%), mitral stenosis (MS) (21%), and aortic stenosis (AS) (15%). The z scores of the GLS and LVMI and severity scores of the MS, MR, AS, and AR were all positively correlated with increasing age (p < 0.05). Twenty patients (38%) had a left ventricular remodeling pattern. Conclusions: The most significant left ventricular myocardial deformation, hypertrophy and valvular heart disease were observed in the patients with MPS VI, II, and I, followed by those with MPS IV; in contrast, patients with MPS III had the mildest manifestations. Cardiac abnormalities in patients with MPS worsened with increasing age in accordance with the progressive nature of this disease.

scholarly journals Relationships among Height, Weight, Body Mass Index, and Age in Taiwanese Children with Different Types of Mucopolysaccharidoses

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 148 ◽  
Author(s):  
Hsiang-Yu Lin ◽  
Chung-Lin Lee ◽  
Pao Chin Chiu ◽  
Dau-Ming Niu ◽  
Fuu-Jen Tsai ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Growth Retardation ◽  
Clinical Manifestations ◽  
Mps Ii ◽  
Mps Vi ◽  
Z Scores ◽  
Mps Iva ◽  
Mps I ◽  
Mps Iii

Background: Children with mucopolysaccharidosis (MPS) generally appear unaffected at birth but may develop multiple clinical manifestations including profound growth impairment as they grow older. Each type of MPS has a variable age at onset and variable rate of progression, however, information regarding growth in Asian children is limited. Methods: This retrospective analysis included 129 Taiwanese patients with MPS (age range, 0.7 to 19.5 years, median age, 7.9 years) from eight medical centers in Taiwan from January 1996 through December 2018. Results: The mean z scores for the first recorded values of height, weight, and body mass index in the patients’ medical records were −4.25, −1.04, and 0.41 for MPS I (n = 9), −2.31, 0.19, and 0.84 for MPS II (n = 49), −0.42, 0.08, and −0.12 for MPS III (n = 27), −6.02, −2.04, and 0.12 for MPS IVA (n = 30), and −4.46, −1.52, and 0.19 for MPS VI (n = 14), respectively. MPS IVA had the lowest mean z scores for both height and weight among all types of MPS, followed by MPS VI, MPS I, MPS II, and MPS III, which showed the mildest growth retardation. Both z scores for height and weight were negatively correlated with increasing age for all types of MPS (p < 0.01). Of 32 patients younger than 5 years of age, 16 (50%), and 23 (72%) had positive z scores of height and weight, respectively. A substantial number of younger patients with MPS I, II, III, and IVA had a positive height z score. The median age at diagnosis was 3.9 years (n = 115). Conclusions: The patients with MPS IVA had the most significant growth retardation among all types of MPS, followed by MPS VI, MPS I, MPS II, and MPS III. The height and weight of the MPS patients younger than 2–5 years of age were higher than those of healthy individuals, however, their growth significantly decelerated in subsequent years. Understanding the growth curve and potential involved in each type of MPS may allow for early diagnosis and timely management of the disease, which may improve the quality of life.

scholarly journals Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 155 ◽  
Author(s):  
Galina Baydakova ◽  
Alex Ilyushkina ◽  
Lidia Gaffke ◽  
Karolina Pierzynowska ◽  
Igor Bychkov ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Fabry Disease ◽  
Direct Result ◽  
Control Group ◽  
Lysosomal Storage ◽  
Mps Ii ◽  
Mps Vi ◽  
Mps I ◽  
Mps Iii

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage disorders associated with impaired glycosaminoglycans (GAGs) catabolism. In MPS I, II, III, and VII, heparan sulfate (HS) cannot be degraded because of the lack of sufficient activity of the respective enzymes, and its accumulation in the brain causes neurological symptoms. Globotriaosylsphingosine (LysoGb3), the deacylated form of globotriaosylceramide (Gb3), is described as a highly sensitive biomarker for another lysosomal storage disease—Fabry disease. The connection between MPSs and LysoGb3 has not yet been established. This study included 36—MPS I, 15—MPS II, 25—MPS III, 26—MPS IV, and 14—MPS VI patients who were diagnosed by biochemical and molecular methods and a control group of 250 males and 250 females. The concentration of lysosphingolipids (LysoSLs) was measured in dried blood spots by high pressure liquid chromatography—tandem mass spectrometry. We have demonstrated that LysoGb3 concentration was significantly elevated (p < 0.0001) in untreated MPS I (3.07 + 1.55 ng/mL), MPS II (5.24 + 2.13 ng/mL), and MPS III (6.82 + 3.69 ng/mL) patients, compared to the control group (0.87 + 0.55 ng/mL). LysoGb3 level was normal in MPS VI and MPS IVA (1.26 + 0.39 and 0.99 + 0.38 ng/mL, respectively). Activity of α-galactosidase A (α-Gal A), an enzyme deficient in Fabry disease, was not, however, inhibited by heparan sulfate in vitro, indicating that an increase of LysoGb3 level in MPS I, MPS II, and MPS III is an indirect effect of stored MPSs rather than a direct result of impairment of degradation of this compound by HS. Our findings indicate some association of elevated LysoGb3 concentration with the neuronopathic forms of MPSs. The pathological mechanism of which is still to be studied.

scholarly journals Roentgenographic diagnosis of mucopolysaccharidosis with particular reference to Morquio syndrome

2012 ◽  
Vol 16 (1) ◽  
pp. 32-34 ◽  
Author(s):  
Umesh Chandra Parashari ◽  
Sachin Khanduri ◽  
Samarjit Bhadury ◽  
Sugandha Rawat
Keyword(s):  
Autosomal Recessive ◽  
Dysostosis Multiplex ◽  
Mps Ii ◽  
Hurler’S Syndrome ◽  
Morquio Syndrome ◽  
Hunter's Syndrome ◽  
Mps I ◽  
Mps Iii ◽  
Skeletal Findings ◽  
Sanfilippo's Syndrome

Mucopolysaccharidosis (MPS) comprises a group of conditions associated with an abnormality in glycoprotein or mucopolysaccharides metabolism. Types of MPS identified are MPS I-H (Hurler's syndrome, gargoylism), MPS II (Hunter's syndrome), MPS III (Sanfilippo's syndrome), MPS IV (Morquio-Brailsford syndrome), MPS I-S (Scheie's syndrome) and MPS VI (Maroteaux-Lamy syndrome). The Hunter type is inherited as an X-linked recessive; the others are autosomal recessive. Patients with MPS IV can usually be clinically distinguished from patients with other forms of MPS; their intelligence is unimpaired, in contrast with other forms of MPS. Husler coined the term dysostosis multiplex to describe the skeletal findings.

scholarly journals Differences in MPS I and MPS II Disease Manifestations

2021 ◽  
Vol 22 (15) ◽  
pp. 7888
Author(s):  
Christiane S. Hampe ◽  
Brianna D. Yund ◽  
Paul J. Orchard ◽  
Troy C. Lund ◽  
Jacob Wesley ◽  
...  
Keyword(s):  
Dermatan Sulfate ◽  
Treatment Options ◽  
Neurological Involvement ◽  
Type I ◽  
Ionic Balance ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Corneal Clouding ◽  
Mps I

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

Abstract 18498: Description of Aortic Root Growth and Outcomes in a Cohort of Pediatric Patients with Loeys-Dietz Syndrome

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Nitya Viswanathan ◽  
Shaine A Morris
Keyword(s):  
Aortic Dissection ◽  
Root Growth ◽  
Aortic Root ◽  
Aortic Surgery ◽  
Genetic Mutation ◽  
Root Diameter ◽  
Adverse Outcomes ◽  
Rate Of Change ◽  
Z Score ◽  
Repeat Surgery

Background: Loeys Dietz Syndrome (LDS) is associated with rapid aortic dilation and aortic dissection, but data on children with LDS are limited. The goal of this study is to describe aortic root growth and outcomes in children with LDS. Methods: Patients with LDS were identified from an institutional database. Data regarding genetic mutation, medications, aortic root dimensions by transthoracic echocardiography (TTE), aortic dissection and surgical intervention were collected. For those with >2 TTEs 1 year apart, rate of change in z-score was calculated using linear regression. TTEs performed after aortic surgery were excluded. We examined if variables were associated with rate of aortic root growth. Results: Of 16 patients, 8 were female. Five had a TGFBR1 and 9 had a TGFBR2 mutation; 2 patients did not have genetic data available. Median aortic root Z-score at diagnosis was 3.5 (range 0.5-25.4). Fifteen patients were on medication (2 beta-blocker (BB), 5 angiotensin receptor blocker (ARB), 5 BB+ARB, and 3 with past use of both). Four patients underwent prophylactic root replacement at ages 3.3, 6.7, 8.7, and 9.4 years at root dimensions 3.2, 6.5, 4.0, and 4.1 cm respectively. One patient had a Type A dissection at age 15y after prior root replacement and underwent repeat surgery. Another underwent heart transplant at 6.9 years old after prior root replacement. Ten patients had serial TTE data. Median change in aortic root diameter and Z-score was 0.11cm/year and 0.1/year respectively. Mean change in z-score per year for those on on BB was -0.1± (range -1.2 to 0.7), ARB 0.5 (range 0.1 to 1.1) and both 0.0 (range -0.2 to 0.2, p=NS). No variables studied were associated with faster aortic growth. Conclusions: Degree of aortic root dilation and rate of aortic root growth is highly variable in children with LDS, although factors associated more aggressive disease are unclear. The high proportion of patients with adverse outcomes including aortic dissection and surgery is concerning.

Mucopolysaccharidoses

2019 ◽  
pp. 79-82
Author(s):  
Kevin B. Hoover
Keyword(s):  
Stem Cell ◽  
Soft Tissues ◽  
Lysosomal Storage Diseases ◽  
Appendicular Skeleton ◽  
Lysosomal Storage ◽  
Storage Diseases ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Spine Mri ◽  
Mps I

Chapter 84 discusses mucopolysaccharidoses, which are genetic, lysosomal storage diseases resulting in the accumulation of glycosaminoglycans (GAG) in the soft tissues. Musculoskeletal complications of mucopolysaccharidosis (MPS) are common beginning in childhood. These result from abnormal ossification and periarticular GAG accumulation. Radiographs of the axial and appendicular skeleton (skeletal survey) are used for the baseline assessment of MPS disease. Progression of skeletal abnormalities is monitored with annual cervical spine MRI. Stem cell transplantation is the treatment of choice in MPS I, and enzyme replacement therapy (ERT) is the treatment of choice in MPS I Hurler-Scheie and Scheie, MPS II, and MPS VI.

Heparan sulfate and dermatan sulfate disaccharide levels for newborn screening in MPS I, MPS II and MPS III

2013 ◽  
Vol 108 (2) ◽  
pp. S95
Author(s):  
Naomi van Vlies ◽  
Jessica de Ruijter ◽  
Minke de Ru ◽  
Tom Wagemans ◽  
Lodewijk IJlst ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Heparan Sulfate ◽  
Dermatan Sulfate ◽  
Mps Ii ◽  
Mps I ◽  
Mps Iii

scholarly journals Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1347
Author(s):  
Nivethitha Arunkumar ◽  
Dung Chi Vu ◽  
Shaukat Khan ◽  
Hironori Kobayashi ◽  
Thi Bich Ngoc Can ◽  
...  
Keyword(s):  
Lysosomal Enzymes ◽  
Dermatan Sulfate ◽  
Clinical Manifestations ◽  
Combination Method ◽  
High Risk Population ◽  
Combined Method ◽  
Mps Ii ◽  
Mps Vi ◽  
Mps Iva ◽  
Mps I

Mucopolysaccharidoses (MPS) and mucolipidosis (ML II/III) are a group of lysosomal storage disorders (LSDs) that occur due to a dysfunction of the lysosomal hydrolases responsible for the catabolism of glycosaminoglycans (GAGs). However, ML is caused by a deficiency of the enzyme uridine-diphosphate N-acetylglucosamine:lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. A timely diagnosis of MPS and ML can lead to appropriate therapeutic options for patients. To improve the accuracy of diagnosis for MPS and ML in a high-risk population, we propose a combination method based on known biomarkers, enzyme activities, and specific GAGs. We measured five lysosomal enzymes (α-L-iduronidase (MPS I), iduronate-2-sulfatase (MPS II), α-N-acetylglucosaminidase (MPS IIIB), N-acetylglucosamine-6-sulfatase (MPS IVA), and N-acetylglucosamine-4-sulfatase (MPS VI)) and five GAGs (two kinds of heparan sulfate (HS), dermatan sulfate (DS), and two kinds of keratan sulfate (KS)) in dried blood samples (DBS) to diagnose suspected MPS patients by five-plex enzyme and simultaneous five GAGs assays. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) for both assays. These combined assays were tested for 43 patients with suspected MPS and 103 normal control subjects. We diagnosed two MPS I, thirteen MPS II, one MPS IIIB, three MPS IVA, two MPS VI, and six ML patients with this combined method, where enzymes, GAGs, and clinical manifestations were compatible. The remaining 16 patients were not diagnosed with MPS or ML. The five-plex enzyme assay successfully identified MPS patients from controls. Patients with MPS I, MPS II, and MPS IIIB had significantly elevated HS and DS levels in DBS. Compared to age-matched controls, patients with ML and MPS had significantly elevated mono-sulfated KS and di-sulfated KS levels. The results indicated that the combination method could distinguish these affected patients with MPS or ML from healthy controls. Overall, this study has shown that this combined method is effective and can be implemented in larger populations, including newborn screening.

scholarly journals Carpal tunnel syndrome in pediatric mucopolysaccharidoses

2015 ◽  
Author(s):  
Trupti Mangesh Jadhav ◽  
Andrew J Kornberg ◽  
Heidi Peters ◽  
Joy Lee ◽  
Monique M Ryan
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Median Nerve ◽  
Carpal Tunnel ◽  
Hand Function ◽  
Significant Loss ◽  
Mps Ii ◽  
Tunnel Syndrome ◽  
Median Nerve Decompression ◽  
Mps I ◽  
Mps Iii

BackgroundCarpal tunnel syndrome (CTS) is rare in children but is a recognised complication of the mucopolysaccharidoses (MPS). Clinicians should have a low threshold of suspicion for CTS in this group as symptoms may be atypical or minimal. If untreated, CTS can cause significant loss of hand function. We present findings in 11 children with mucopolysaccharidoses and suspected CTS, and propose guidelines for screening for CTS in children with these disorders.MethodsClinical and electrodiagnostic data of 11 children with mucopolysaccharidoses, who were suspected on clinical grounds to have CTS, was reviewed. All subjects underwent motor and sensory conduction studies of bilateral median and ulnar nerves. The presence of carpal tunnel syndrome and its severity was determined. Subsequent details of intervention(s) and recurrence were noted.ResultsThree children had MPS I, five had MPS II, one had MPS III and two had MPS IV. Seven had motor and three sensory features referable to median nerve compression. Nine of the eleven children (2/3 with MPS I, 5/5 with MPS II, 0/1 with MPS III, 2/2 with MPS IV) had median neuropathies at the wrist, (eight bilateral, one unilateral) which were mild in three, moderate in five, and severe in one. Three children presented with symptoms at five years age. Six underwent median nerve decompression. Four of these had recurrent symptoms several years after surgery, which was confirmed on nerve conduction studies in two cases. To the best of our knowledge, this is the first report of carpal tunnel syndrome in MPS IV. ConclusionSome children with mucopolysaccharidoses experience early development of at least moderately severe carpal tunnel syndrome. We recommend screening for median neuropathies at the wrist from age 5 years for children with mucopolysaccharidoses, particularly types I, II and IV, regardless of their symptoms of CTS, and of the treatment received for mucopolysaccharidosis.

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