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

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.

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Diagnosis of Mucopolysaccharidoses and Mucolipidosis by Assaying Multiplex Enzymes and Glycosaminoglycans

Diagnostics ◽

10.3390/diagnostics11081347 ◽

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.

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

Diagnostics ◽

10.3390/diagnostics10020062 ◽

2020 ◽

Vol 10 (2) ◽

pp. 62 ◽

Cited By ~ 1

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.

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

Diagnostics ◽

10.3390/diagnostics11010016 ◽

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.

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Elevated LysoGb3 Concentration in the Neuronopathic Forms of Mucopolysaccharidoses

Diagnostics ◽

10.3390/diagnostics10030155 ◽

2020 ◽

Vol 10 (3) ◽

pp. 155 ◽

Cited By ~ 1

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.

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Differential effects of body mass index on domain-specific cognitive outcomes after stroke

Scientific Reports ◽

10.1038/s41598-021-93714-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Minwoo Lee ◽

Mi Sun Oh ◽

San Jung ◽

Ju-Hun Lee ◽

Chul-Ho Kim ◽

...

Keyword(s):

Body Mass Index ◽

Ischemic Stroke ◽

Cognitive Function ◽

Frontal Lobe ◽

Body Mass ◽

Cognitive Outcomes ◽

Stroke Survivors ◽

Word Fluency ◽

Domain Specific ◽

Z Scores

AbstractAlthough the obesity paradox is an important modifiable factor in cardiovascular diseases, little research has been conducted to determine how it affects post-stroke cognitive function. We aimed to investigate the association between body mass index (BMI) and domain-specific cognitive outcomes, focusing on the subdivision of each frontal domain function in post-ischemic stroke survivors. A total of 335 ischemic stroke patients were included in the study after completion of the Korean-Mini Mental Status Examination (K-MMSE) and the vascular cognitive impairment harmonization standards neuropsychological protocol at 3 months after stroke. Frontal lobe functions were analyzed using semantic/phonemic fluency, processing speed, and mental set shifting. Our study participants were categorized into four groups according to BMI quartiles. The z-scores of K-MMSE at 3 months differed significantly between the groups after adjustment for initial stroke severity (p = 0.014). Global cognitive function in stroke survivors in the Q1 (the lowest quartile) BMI group was significantly lower than those in Q2 and Q4 (the highest quartile) BMI groups (K-MMSE z-scores, Q1: − 2.10 ± 3.40 vs. Q2: 0.71 ± 1.95 and Q4: − 1.21 ± 1.65). Controlled oral word association test findings indicated that phonemic and semantic word fluency was lower in Q4 BMI group participants than in Q2 BMI group participants (p = 0.016 and p = 0.023 respectively). BMI might differentially affect cognitive domains after ischemic stroke. Although being underweight may negatively affect global cognition post-stroke, obesity could induce frontal lobe dysfunctions, specifically phonemic and semantic word fluency.

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54 Body Mass Index vs Weight-for-Length in Infancy and Cardiometabolic Outcomes at Age 8-10 Years

Paediatrics & Child Health ◽

10.1093/pch/pxab061.043 ◽

2021 ◽

Vol 26 (Supplement_1) ◽

pp. e39-e39

Author(s):

Jean-Baptiste Roberge ◽

Soren Harnois-Leblanc ◽

Vanessa McNealis ◽

Andraea van Hulst ◽

Tracie A Barnett ◽

...

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Predictive Ability ◽

Subject Area ◽

Overweight And Obesity ◽

Growth Monitoring ◽

Linear Regression Models ◽

Eta Squared ◽

Z Scores ◽

Using Data

Abstract Primary Subject area Public Health and Preventive Medicine Background The WHO provides body mass index (BMI) curves for infants 0 to < 2 years old, but how these compare to the recommended method (weight-for-length [WFL]) in predicting later adiposity and cardiometabolic measures is uncertain. Objectives Our project aimed to: 1) confirm that WFL and BMI in infancy are associated with adiposity and cardiometabolic measures at 8-10 years old; and 2) compare the predictive ability of the two methods. We hypothesized that both methods would perform similarly. Design/Methods WFL and BMI Z-scores (zWFL and zBMI) at 6, 12, and 18 months of age were computed using data extracted from health booklets, used among participants in a prospective cohort study investigating the natural history of obesity and cardiovascular risk in youth (n = 464). Outcome measures at 8-10 years included adiposity, lipid profile, blood pressure, and insulin dynamics. The relationships between zWFL, zBMI, and each outcome were estimated using multivariable linear regression models. Outcome prediction at 8-10 years was compared between the two methods, using eta-squared and Lin’s concordance correlation. Results zWFL and zBMI were associated with all measures of adiposity at 8-10 years. Associations with other cardiometabolic measures were less consistent. For both zWFL and zBMI across infancy, eta-squared were highly similar and the Lin’s coefficients were markedly high (> 0.991) for all outcomes. Conclusion zBMI measured in infants appeared to be equivalent to zWFL for predicting adiposity and cardiometabolic measures in childhood. This lends support to the sole use of zBMI for growth monitoring and screening of overweight and obesity from birth to 18 years.

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Correlation of body mass index Z -scores with glucose and lipid profiles among overweight and obese children and adolescents

Jornal de Pediatria ◽

10.1016/j.jped.2017.06.012 ◽

2018 ◽

Vol 94 (3) ◽

pp. 308-312 ◽

Cited By ~ 3

Author(s):

Carlos Alberto Nogueira-de-Almeida ◽

Elza Daniel de Mello

Keyword(s):

Body Mass Index ◽

Children And Adolescents ◽

Body Mass ◽

Lipid Profiles ◽

Obese Children ◽

Z Scores

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Age and body mass index affect fit of spirometry GLI references in schoolchildren

10.1101/2021.10.07.21264678 ◽

2021 ◽

Author(s):

Rebeca Mozun ◽

Cristina Ardura-Garcia ◽

Eva S. L. Pedersen ◽

Jakob Usemann ◽

Florian Singer ◽

...

Keyword(s):

Body Mass Index ◽

Lung Function ◽

Body Mass ◽

Clinical Decision Making ◽

Clinical Care ◽

Normal Weight ◽

Linear Regression Models ◽

Cross Sectional ◽

Mean Values ◽

Z Scores

AbstractBackgroundReferences from the Global Lung Function Initiative (GLI) are widely used to interpret children’s spirometry results. We assessed fit for healthy schoolchildren.MethodsLuftiBus in the school (LUIS) is a population-based cross-sectional study done from 2013-2016 in the canton of Zurich, Switzerland. Parents and children aged 6-17 years answered questionnaires about respiratory symptoms and lifestyle. Children underwent spirometry in a mobile lung function lab. We calculated GLI-based z-scores for FEV1, FVC, FEV1/FVC, and FEF25-75 for healthy White participants. We defined appropriate fit to GLI references by mean values ±0.5 z-scores. We assessed if fit varied by age, body mass index, height, and sex using linear regression models.ResultsWe analysed data from 2036 children with valid FEV1 measurements of which 1762 also had valid FVC measurements. The median age was 12.2 years. Fit was appropriate for children aged 6-11 years for all indices. In adolescents aged 12-17 years, fit was appropriate for FEV1/FVC (mean: -0.09; SD: 1.02) z-scores, but not for FEV1 (mean: -0.62; SD: 0.98), FVC (mean: -0.60; SD: 0.98), and FEF25-75 (mean: -0.54; SD: 1.02). FEV1, FVC, and FEF25-75 z-scores fitted better in children considered overweight (means: -0.25, -0.13, -0.38) than normal weight (means: -0.55, -0.50, -0.55; p-trend: <0.001, 0.014, <0.001). FEV1, FVC, and FEF25-75 z-scores depended on both age and height (p interaction: 0.034, 0.019, <0.01).ConclusionGLI-based FEV1, FVC, and FEF25-75 z-scores do not fit White Swiss adolescents well. This should be considered when using reference equations for clinical decision making, research and international comparison.Take home messageOur study suggests GLI-based FEV1, FVC, and FEF25-75 z-scores over detect abnormal lung function in Swiss adolescents, and more so among slimmer adolescents, which has important implications for clinical care, research, and international comparisons.

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