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Abstract Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration. MPS II-iPSCs were successfully differentiated into cortical neurons with characteristic biochemical and cellular phenotypes, including axonal beadings positive for phosphorylated tau, and unique electrophysiological abnormalities, which were mostly rescued in ISO-iPSC-derived neurons. RNA sequencing analysis uncovered dysregulation in three major signaling pathways, including Wnt/β-catenin, p38 MAP kinase, and calcium pathways, in mature MPS II neurons. Further mechanistic characterization indicated that the dysregulation in calcium signaling led to an elevated intracellular calcium level, which might be linked to compromised survival of neurons. Based on these dysregulated pathways, several related chemicals and drugs were tested using this mature MPS II neuron-based platform and a small-molecule glycogen synthase kinase-3β inhibitor was found to significantly rescue neuronal survival, neurite morphology, and electrophysiological abnormalities in MPS II neurons. Our results underscore that the MPS II-iPSC-based platform significantly contributes to unraveling the mechanisms underlying the degeneration and death of MPS II neurons and assessing potential drug candidates. Furthermore, the study revealed that targeting the specific dysregulation of signaling pathways downstream of GAG accumulation in MPS II neurons with a well-characterized drug could potentially ameliorate neuronal degeneration.

Abstract Background We clinically and genetically evaluated a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. Whole‐exome sequencing revealed a de novo gain‐of‐function variant, p.Tyr715Cys, in the C‐terminal domain of ClC‐7 encoded by CLCN7. Methods Nicoli et al. (2019) assessed the functional impact of p.Tyr715Cys by heterologous expression in Xenopus oocytes and evaluating resulting currents. Results The variant led to increased outward currents, indicating it underlies the patient's phenotype of lysosomal hyperacidity, storage defects and vacuolization. This demonstrates the crucial physiological role of ClC‐7 antiporter activity in maintaining appropriate lysosomal pH. Conclusion Elucidating mechanisms by which CLCN7 variants lead to lysosomal dysfunction will advance understanding of genotype–phenotype correlations. Identifying modifier genes and compensatory pathways may reveal therapeutic targets. Ongoing functional characterization of variants along with longitudinal clinical evaluations will continue advancing knowledge of ClC‐7's critical roles and disease mechanisms resulting from its dysfunction. Expanded cohort studies are warranted to delineate the full spectrum of associated phenotypes.

BackgroundMuscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.MethodsThis study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification–negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).ResultsWES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.ConclusionWES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

Kabuki syndrome (KS) is a rare genetic disorder characterized by distinct facial features, intellectual disability, and multiple congenital anomalies. We conducted a comprehensive analysis of the genetic and phenotypic spectrum of KS in a Taiwanese patient group of 23 patients. KMT2D variants were found in 22 individuals, with missense (26.1%), nonsense (21.7%), and frameshift (17.4%) variants being the most prevalent. One patient had a KMT2D variant of uncertain significance. The most common clinical characteristics included distinct facial features (100%), intellectual disability (100%), developmental delay (95.7%), speech delay (78.3%), hypotonia (69.6%), congenital heart abnormalities (69.6%), and recurrent infections (65.2%). Other abnormalities included hearing loss (39.1%), seizures (26.1%), cleft palate (26.1%), and renal anomalies (21.7%). This study broadens the mutational and phenotypic spectrum of KS in the Taiwanese population, highlighting the importance of comprehensive genetic testing and multidisciplinary clinical evaluations for diagnosis and treatment.

Congenital heart defects (CHDs) affect a substantial proportion of patients with Kabuki syndrome. However, the prevalence and type of CHD and the genotype–phenotype correlations in Asian populations are not fully elucidated. This study performed a retrospective analysis of 23 Taiwanese patients with molecularly confirmed Kabuki syndrome. Twenty-two patients presented with pathogenic variants in the KMT2D gene. Comprehensive clinical assessments were performed. A literature review was conducted to summarize the spectrum of CHDs in patients with Kabuki syndrome. In total, 16 (73.9%) of 22 patients with pathogenic KMT2D variants had CHDs. The most common types of CHD were atrial septal defects (37.5%), ventricular septal defects (18.8%), coarctation of the aorta (18.8%), bicuspid aortic valve (12.5%), persistent left superior vena cava (12.5%), mitral valve prolapse (12.5%), mitral regurgitation (12.5%), and patent ductus arteriosus (12.5%). Other cardiac abnormalities were less common. Further, there were no clear genotype–phenotype correlations found. A literature review revealed similar patterns of CHDs, with a predominance of left-sided obstructive lesions and septal defects. In conclusion, the most common types of CHDs in Taiwanese patients with Kabuki syndrome who presented with KMT2D mutations are left-sided obstructive lesions and septal defects.

Background: Small population group-based cohorts have found that perinatal factors may contribute to the development of asthma in children. We aimed to investigate maternal and neonatal risk factors for the asthma phenotypes using two databases from the Taiwan's Maternal and Child Health Database (TMCHD) and the National Health Insurance Research Database (NHIRD). Methods: Perinatal data was obtained from 2004 to 2008 in the TMCHD and linked the NHIRD to obtain relevant medical information regarding maternal and neonatal risk factors of three asthma phenotypes which were identified as transient early asthma, persistent asthma, and late-onset asthma. A multivariate logistic regression analysis was conducted to adjust for covariates. Results: The percentage of non-asthmatic patients was 77.02% and asthmatic (transient early asthma, late onset asthma, and persistent asthma) patients were 8.96%, 11.64%, and 2.42%, respectively. Maternal risk factors—including Cesarean section, maternal asthma, maternal allergic rhinitis (AR), and premature rupture of membranes—and neonatal risk factors, such as male gender, gestational age 29–37 weeks, ventilator use, antibiotics use, AR, and atopic dermatitis, were associated with the development of these three asthma phenotypes. Twins and a gestational age of 28 weeks or less premature were associated with the development of transient early asthma and persistent asthma, but not late onset asthma. Triplets and above were associated with the development of transient early asthma, but not late onset or persistent asthma. Conclusion: Various asthma phenotypes have different risk factors; therefore, their distinct risk factors should be identified in order to early diagnosis and treatment.

The present study included the first case of mucopolysaccharidosis (MPS) type VII in Taiwan. During pregnancy, the patient was diagnosed with hydrops fetalis and had ascites aspiration 4 times. In the following years, she presented gradually with chronic lung disease, developmental delay, short stature, dysmorphic features of coarse face, macroglossia and pigeon chest with scoliosis. Upon referral at age 4 years, she had corneal clouding, mild limitation of range of motion (ROM) and hepatosplenomegaly. X-ray showed paddle ribs and dysplastic vertebral bodies. MPS was suspected and urine glycosaminoglycans (GAGs) elevated were noted. The leukocyte enzymatic analyses for MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI were all normal. Afterward, the molecular analysis showed two heterozygous genetic variants of c.104C > A and c.1454C > T in trans in the GUSB gene (NM_000181.4) which were the causes for MPS VII. Then, we checked the leukocyte β-glucuronidase activity for MPS VII and showed extremely low, therefore confirmed the diagnosis. Clinicians should increase the awareness on the early signs of MPS to have a prompt diagnosis and offer the correct treatment like enzyme replacement therapy (ERT) as early as possible.

Objective: We present detection of hypermethylation at H19 differentially methylated region (DMR) at amniocentesis in a fetus with overgrowth, distended abdomen and Beckwith-Wiedemann syndrome (BWS). Case report: A 31-year-old, gravida 2, para 1, woman was referred for genetic counseling at 22 weeks of gestation because of fetal overgrowth with fetal biometry equivalent to 24 weeks of gestation and a distended abdomen with an abdominal circumference equivalent to 26 weeks of gestation. She did not undergo any assisted reproductive technology during this pregnancy. Amniocentesis was performed at 23 weeks of gestation. Conventional cytogenetic analysis revealed a karyotype of 46,XX. Array comparative genomic hybridization analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Methylation analysis on the DNA extracted from amniocytes revealed hypermethylation at H19DMR [imprinting center 1 (IC1)] and normal methylation at KvDMR1 (IC2). The methylation test confirmed the diagnosis of BWS in the fetus. The parents decided to continue the pregnancy. At 36 weeks of gestation, a 4000-g female baby was delivered with macroglossia, ear tags and creases, and an enlarged liver, consistent with the phenotype of BWS. Conclusion: Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of BWS, and methylation analysis of H19DMR (IC1) and KvDMR1 (IC2) is useful under such a circumstance.

Abstract Background Cardiac abnormalities have been observed in patients with mucopolysaccharidosis type II (MPS II). The aim of this study was to investigate the cardiac features and natural progression of Taiwanese patients with MPS II, and evaluate the impact of enzyme replacement therapy (ERT) on cardiac structure and function. Methods The medical records and echocardiograms of 48 Taiwanese patients with MPS II (median age, 6.9 years; age range, 0.1–27.9 years) were reviewed. The relationships between age and each echocardiographic parameter were analyzed. Results The mean z-scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter were 1.10, 2.70, 0.95 and 1.91, respectively. Z scores > 2 were identified in 33%, 54%, 13%, and 46% for LVMI, IVSd, LVPWd, and aortic diameter, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (MR) (56%), followed by aortic regurgitation (AR) (33%). The severity of mitral stenosis (MS), MR, aortic stenosis (AS), AR, and the existence of valvular heart disease were all positively correlated with increasing age (p 0.05). Conclusions High prevalence rates of valvular heart disease and cardiac hypertrophy were observed in the MPS II patients in this study. The existence and severity of cardiac hypertrophy and valvular heart disease in these patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease. ERT for MPS II appeared to be effective in stabilizing or reducing the progression of cardiac hypertrophy, but it only had a limited effect on valvulopathy.

Abstract Background Mucopolysaccharidoses (MPSs) are a group of inherited metabolic diseases, which are characterized by the accumulation of glycosaminoglycans, and eventually lead to the progressive damage of various tissues and organs. Methods An epidemiological study of MPS in Taiwan was performed using multiple sources. The survival and diagnostic age for different types of MPS between 1985 and 2019 were evaluated. Results Between 1985 and 2019, there were 175 patients diagnosed with MPS disorders in the Taiwanese population, with a median diagnostic age of 3.9 years. There were 21 (12%), 78 (45%), 33 (19%), 32 (18%) and 11 (6%) patients diagnosed with MPS I, II, III, IV and VI, respectively, with median diagnostic ages of 1.5, 3.8, 4.7, 4.5 and 3.7 years, respectively. Diagnosis of MPS patients was significantly earlier in recent decades (p

Despite advances in neonatal intensive care in the recent decade, a large number of very preterm infants (VPIs) remain at risk for significant neurodevelopmental impairment (NDI). Given that there are many interventions need to be implemented during the critical perinatal period so that complications of these vulnerable VPIs could be minimized, it is urgent to develop multi-discipline strategies based on evidence to be carried out. The objective of this new term evidence-based perinatal critical strategies (EBPCS), is to provide beneficial intervention towards better neurodevelopmental outcomes, specifically for preterm infants below 28 weeks gestational age. EBPCS is defined as the management of the VPIs during the perinatal period which would include antenatal counseling with team briefing and share decision making, treat the chorioamnionitis, antenatal MgS04, antenatal steroid, delayed cord clamping/milking, neonatal resuscitation team preparation, prevention of hypothermia, immediate respiratory support with continuous positive airway pressure at delivery room, less invasive surfactant administration, early surfactant with budesonide therapy, support of cardiovascular system, early initiate of probiotics administration, early caffeine, early parenteral and enteral nutrition, promptly initiating antibiotics. These critical strategies will be discussed detail in the text; nonetheless, standardized protocols, technical skills and repeated training are the cornerstones of successful of EBPCS. Further experience from different NICU is needed to prove whether these very complicate and comprehensive perinatal critical strategies could translate into daily practice to mitigate the incidence of NDI in high-risk VPIs.

Objective: We present prenatal diagnosis and molecular cytogenetic characterization of an inverted duplication of proximal chromosome 15 [inv dup(15)] presenting as a small supernumerary marker chromosome (sSMC) at amniocentesis associated with concomitant microduplication of 8q22.1. Materials and methods: A 39-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age, and the result was 47, XY, +mar dn. The woman requested for repeat amniocentesis at 20 weeks of gestation. Array comparative genomic hybridization (aCGH), fluorescence in situ hybridization (FISH), quantitative fluorescent polymerase chain reaction (QF-PCR) and DNA methylation analysis were applied to determine the nature of the sSMC.Results: aCGH on the uncultured amniocytes revealed the result of arr 8q22.1 (93,918,763–96,618,539) × 3.0, arr 15q11.2q13.2 (22,765,628–30,658,876) × 4.0, arr 15q13.2q13.3 (30,653,877–32,509,926) × 3.0 [GRCh37 (hg19)]. Interphase FISH analysis using RP11-34H12 [15q13.2; Texas Red, 30,709,033–30,893,021 (hg19)] on 100 uncultured amniocytes showed that 38 cells had three signals, 45 cells had four signals and 27 cells had two signals. The parental bloods had normal aCGH results. The karyotype of cultured amniocytes was 47, XY, +inv dup(15) (pter→q13::q13→pter) which was confirmed by metaphase FISH analysis. No informative markers could be found in QF-PCR analysis. DNA methylation analysis on cord blood confirmed a maternal origin of the 15q11-q13 gene dosage increase with a result of 15q11.2 SNRPN DNA hypermethylation. Postnatal cytogenetic analysis on cord blood, umbilical cord and placenta showed the results consistent with the prenatal diagnosis. Conclusion: Molecular cytogenetic techniques are useful for rapid diagnosis of an inv dup(15) chromosome presenting as an sSMC at amniocentesis.

The ductus arteriosus is likely to close without treatment in most infants born at gestational age (GA) > 28 weeks (73%), and those with birth weight > 1000 g (94%). However, the rates of spontaneous ductal closure among less mature or smaller infants with respiratory distress syndrome are not known. Extremely preterm infants born at GA < 28 weeks are associated with a high risk of severe intraventricular hemorrhage (IVH) or pulmonary hemorrhage, which usually occur within 72 h after birth and affect mortality and long-term neurological development. These serious hemorrhagic complications may be closely related to hemodynamic changes caused by a hemodynamically significant patent ductus arteriosus (hs-PDA). While prophylactic indomethacin has been shown to reduce the rates of PDA, PDA ligation, severe IVH and early pulmonary hemorrhage, the available evidence does not support its prophylactic use in preterm infants. Symptomatic or late treatment is associated with lower success rate, and increased complications of a hs-PDA. The issue of “to treat or not to treat a PDA” is controversial. Considering the relationship between the effectiveness and timing of pharmacological treatment, early targeted treatment may be an alternative approach for the early identification of a hs-PDA in specific high-risk patient population, especially infants

Small supernumerary marker chromosomes (sSMCs) derived from the chromosome 6 short arm are rare and their clinical significance remains unknown. No case with sSMC(6) without centromeric DNA has been reported. Partial trisomy and tetrasomy of distal 6p is a rare but clinically distinct syndrome. We report on a de novo mosaic sSMC causing partial tetrasomy for 6p23-p25.3 in a male infant with symptoms of being small for gestational age, microcephaly, facial dysmorphism, congenital eye defects, and multi-system malformation. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+mar [25]/46,XY [22]. Array comparative genomic hybridization (aCGH) revealed mosaic tetrasomy of distal 6p. This is the first case of mosaic tetrasomy 6p23-p25.3 caused by an inverted duplicated neocentric sSMC with characteristic features of trisomy distal 6p. Comparison of phenotypes in cases with trisomy and tetrasomy of 6p23-p25.3 could facilitate a genotype–phenotype correlation and identification of candidate genes contributing to their presentation. The presentation of anterior segment dysgenesis and anomaly of the renal system suggest triplosensitivity of the FOXC1 gene. In patients with microcephaly growth retardation, and malformation of the cardiac and renal systems, presentation of anterior segment dysgenesis might be indicative of chromosome 6p duplication, and aCGH evaluation should be performed for associated syndromic disease.

SHORT syndrome is a rare, multisystem disease named with the acronym arising from short stature, hyperextensibility of joints, ocular depression, Rieger anomaly, and teething delay. Metabolic anomalies such as insulin resistance and diabetes are also present. This disease is related to heterozygous variants in the PIK3R1 and is inherited in an autosomal-dominant manner. In this case report, we present a Taiwanese boy with SHORT syndrome who had growth retardation and dysmorphic features, including a triangular face, prominent forehead, and small chin. We performed anthropometric and laboratory measurements and imaging examinations. We noted no insulin resistance or diabetes. We performed whole exome and Sanger sequencing and confirmed the underlying genetic variant, detecting a heterozygous variant of PIK3R1 (NM_181523.3) (c.1945C > T). In a family survey, his parents indicated no similar clinical symptoms and no gene variant. This case is the first SHORT syndrome in Taiwan. Specific facial dysmorphisms of this case help us confirm the diagnosis with timely genetic testing and then we can provide appropriate management and proper care.

Background: Unexplained developmental delay or intellectual disability (DD/ID) has an estimated prevalence of about 3%–5% in the general population of Taiwan. Array comparative genomic hybridization (array-CGH) is a high-resolution tool that can detect about 50 Kb chromosome aberrations. A previous study has reported a detection rate of 10%–20% for this array.1 This study aimed to investigate and compare the diagnosis rate for DD/ID using array-CGH and conventional chromosome study in DD/ID patients in Taiwan. Methods: We enrolled 177 patients with DD/ID who underwent array-CGH examination at the MacKay Memory Hospital between June 2010 and September 2017. The copy number variants (CNV) were classified into the following three groups: pathogenic (potential pathologic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance, VOUS), according to the ACMG guideline.2 Results: Of the 177 enrolled patients, 100 (56.5%) were men and 77 (43.5%) were women. Ages ranged from 3 months to 50 years, with a median age of 5.2 years. Total 32.0% (32/100) male patients had pathogenic CNV, and 32.5% (25/77) female patients had pathogenic CNV. The ratio of pathogenic CNV in male and female patients was not significantly different (p = 0.379). The proportions of pathogenic CNV at 18 years of age were 32.3% (31/96), 19.4% (6/31), 34.8% (8/23), 16.7% (2/12), and 66.7% (10/15), respectively. The overall diagnosed rate of DD/ID with pathogenic CNV was 27.7% (49/177) using array-CGH in this study. There were 105 patients with conventional karyotyping and array-CGH data at the same time. Nineteen (18.1%) patients had visible chromosomal abnormality. Total 32/105 (30.5%) patients could find at least one pathogenic CNVs. The array-CGH had a higher diagnosed rate than the conventional karyotyping in clinical application. Conclusions: Although array-CGH could not detect point mutation, balanced translocations, inversions, or low-level mosaicism, the diagnosis rate in clinical application was up to 46.3% and 2.5 times that of conventional karyotyping analysis (18.1%). This study demonstrated that array-CGH is a powerful diagnostic tool and should be the first genetic test instead of conventional karyotyping analysis for patients with unexplained DD/ID. Key Words: array-CGH, chromosomal microarray, developmental delay, intellectual disabilities, Taiwan

Abstract Background Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is caused by a deficiency in one of the four enzymes involved in the lysosomal degradation of heparan sulfate. Cardiac abnormalities have been observed in patients with all types of MPS except MPS IX, however few studies have focused on cardiac alterations in patients with MPS III. Methods We reviewed medical records, echocardiograms, and electrocardiograms of 26 Taiwanese patients with MPS III (five with IIIA, 20 with IIIB, and one with IIIC; 14 males and 12 females; median age, 7.4 years; age range, 1.8–26.5 years). The relationships between age and each echocardiographic parameter were analyzed. Results Echocardiographic examinations (n = 26) revealed that 10 patients (38%) had valvular heart disease. Four (15%) and eight (31%) patients had valvular stenosis or regurgitation, respectively. The most prevalent cardiac valve abnormality was mitral regurgitation (31%), followed by aortic regurgitation (19%). However, most of the cases of valvular heart disease were mild. Three (12%), five (19%) and five (19%) patients had mitral valve prolapse, a thickened interventricular septum, and asymmetric septal hypertrophy, respectively. The severity of aortic regurgitation and the existence of valvular heart disease, aortic valve abnormalities and valvular stenosis were all positively correlated with increasing age (p 2 were identified in 0, 38, 8, and 27% of left ventricular mass index, interventricular septal end-diastolic dimension, left ventricular posterior wall end-diastolic dimension, and aortic diameter, respectively. Electrocardiograms in 11 patients revealed the presence of sinus arrhythmia (n = 3), sinus bradycardia (n = 2), and sinus tachycardia (n = 1). Six patients with MPS IIIB had follow-up echocardiographic data at 1.9–18.1 years to compare with the baseline data, which showed some patients had increased thickness of the interventricular septum, as well as more patients had valvular abnormalities at follow-up. Conclusions Cardiac involvement in MPS III is less common and milder compared with other types of MPS. The existence of valvular heart disease, aortic valve abnormalities and valvular stenosis in the patients worsened with increasing age, reinforcing the concept of the progressive nature of this disease.

Abstract Background Most patients with isolated methylmalonic acidemia (MMA) /propionic acidemia (PA) presenting during the neonatal period with acute metabolic distress are at risk for death and significant neurodevelopmental disability. The nationwide newborn screening for MMA/PA has been in place in Taiwan from January, 2000 and data was collected until December, 2016. Results During the study period, 3,155,263 newborns were screened. The overall incidence of MMA mutase type cases was 1/121,356 (n = 26), 1 cobalamin B was detected and that for PA cases (n = 4) was 1/788,816. The time of referral is 8.8 days for MMA patients, and 7.5 days for PA patients. The MMA mutase type patients have higher AST, ALT, and NH3 values as well as a lower pH value (p

Costello syndrome (CS) is a type of RASopathy caused mainly by de-novo heterozygous pathogenic variants in the HRAS gene located on chromosome 11p15.5. The phenotype of CS is characterized by prenatal overgrowth, postnatal failure to thrive, curly or sparse fine hair, coarse facial features, and multisystem involvement, including cardiovascular, endocrine, and gastroenterological disorders. We present a one-year-old girl with rapid weight loss and severe failure to thrive. She had gastroesophageal reflux at the age of four months with subsequent rapid weight loss. The loss of fat tissue over the whole body, refractory to a hypercaloric diet, mimicked the presentation of progressive lipodystrophy and masked the dysmorphic features of CS. The final diagnosis of CS was made by whole exome sequencing, which demonstrated a hot-spot, heterozygouspathogenic variant in the HRAS gene (c.34G > A, rs104894229). Our patient illustrates that the excessive energy needs in CS patients may lead to severe failure to thrive and cause challenges in diagnosing CS. This case also highlights the importance of recognizing CS in patients with a history of prenatal overgrowth, polyhydramnios presenting with severe failure to thrive refractory to pharmacotherapy and tube feeding.

Abstract Background Cardiac abnormalities have been observed in patients with mucopolysaccharidosis (MPS) of any type, with the most documented abnormalities being valvular heart disease and cardiac hypertrophy. However, few studies have focused on the cardiac features of MPS IVA. Methods We reviewed the medical records, echocardiograms, and electrocardiograms of 32 Taiwanese patients with MPS IVA (16 males and 16 females; median age, 10.8 years; age range, 1.1 to 29.1 years) as well as the echocardiographic data of six patients who received enzyme replacement therapy (ERT) for 3–6 years. Results Echocardiographic examinations (n = 32) revealed mean z scores of left ventricular mass index (LVMI), interventricular septum diameter in diastole (IVSd), left ventricular posterior wall diameter in diastole (LVPWd), and aortic diameter of 0.94, 2.70, 0.39, and 3.26, respectively. Z scores > 2 were identified in 25%, 50%, 29%, and 69% of the LVMI, IVSd, LVPWd, and aortic diameter values, respectively. Diastolic dysfunction [reversed ratio between early and late (atrial) ventricular filling velocity (E/A ratio

Chorioamnionitis is a common cause of preterm birth and may cause adverse neonatal outcomes, including neurodevelopmental sequelae. Chorioamnionitis has been marked to a heterogeneous setting of conditions characterized by infection or inflammation or both, followed by a great variety in clinical practice for mothers and their newborns. Recently, a descriptive term: “intrauterine inflammation or infection or both” abbreviated as “Triple I” has been proposed by a National Institute of Child Health and Human Development expert panel to replace the term chorioamnionitis. It is particularly important to recognize that an isolated maternal fever does not automatically equate to chorioamnionitis. This article will review the current literature on chorioamnionitis, and introduce the concept of Triple I, as well as recommendations for assessment and management of pregnant women and their newborns with a diagnosis of Triple I.

Abstract Background Mucopolysaccharidosis type II (MPS II) is the most frequently occurring MPS in Taiwan, with an incidence of 2.05 per 100,000 live male births, but little is known about clinical characteristics and surgical history in Taiwanese patients. Methods Medical history, demographics, signs and symptoms, and surgical history were analysed in all patients from Taiwanese centres in the Hunter Outcome Survey (HOS; NCT 03292887), a global, multicentre registry that collects real-world data on patients with MPS II. Results As of January 2016, 61 male Taiwanese patients were enrolled; 49% (24/49) had received at least one infusion of idursulfase. Median (10th, 90th percentiles) ages at signs and symptom onset and at diagnosis were 2.5 (0.2, 5.5) years (n = 55) and 3.5 (1.2, 11.9) years (n = 56), respectively. Hernia, facial features consistent with MPS II and claw hands were the earliest presenting signs and symptoms (median ages of 3.2 [0.4, 12.0] years, 4.3 [1.1, 12.0] years and 4.7 [2.5, 12.2] years [n = 45, 53 and 50], respectively). More than 75% of patients had undergone a surgical procedure, most commonly hernia repair (57% of patients). Median age at first surgery for hernia repair was 4.2 (0.5, 9.8) years (n = 35). Almost one-third (31.1%) of patients had at least one surgical procedure before diagnosis, and of the 20 procedures before diagnosis, 16 were hernia repair. Conclusions This information from patients in HOS highlights the importance of both medical and surgical history in diagnosing MPS II in Taiwanese patients.

Abstract Background Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis. Methods From August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent α-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed. Results Normal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C > T, c.1025A > G, and c.311A > T) and four with two missense mutations of the IDUA gene (C.300-3C > G, c.1874A > C; c.1037 T > G, c.1091C > T) showed significant deficiencies in IDS and IDUA enzyme activities (

Background: Previous studies have identified preterm birth and/or small for gestational age (SGA) as risk factors for features of the metabolic syndrome, including high blood pressure, insulin sensitivity and atherosclerosis, occurring later in life, with controversial results. We conducted this population-based cohort study to investigate metabolic outcomes in those with former preterm birth and/or SGA status in Taiwan. Methods: Data were obtained from Taiwan's universal National Health Insurance Research Database. From 1996 to 2004, 37,119 preterm infants, 3386 SGA infants, and 162,020 matched controls were included. We investigated the risk of the metabolic disease, including hypertension, diabetes, and hyperlipidemia, which had been recorded by the end of 2008. Results: The preterm and SGA cohort, combined into one, had a significantly increased risk of developing metabolic disorders when compared with the comparison cohort (HR = 2.46, 95% CI = 2.02–3.01). We observed that children with former preterm and SGA status in Taiwan had a higher risk of developing hypertension (HR = 3.24, 95% CI = 1.58–6.67), Type 1 diabetes mellitus (HR = 1.80, 95% CI = 1.05–3.07), Type 2 diabetes mellitus (HR = 2.49, 95% CI = 1.98–3.14), and hyperlipidemia (HR = 2.14, 95% CI = 1.29–3.52). Conclusion: Our study revealed the risk of metabolic disease in those with preterm birth and/or SGA. Further studies with a longer duration of follow-up are required to confirm if there is a tendency for the metabolic syndrome to develop in this study cohort. Key Words: metabolic outcome, preterm birth, small for gestational age (SGA)

Background and Objectives: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNVs) and is recommended for the initial genetic testing of patients with autism spectrum disorder (ASD). This study aims to determine the diagnostic yield of array comparative genomic hybridization (array-CGH) in ASD patients from a cohort of Chinese patients in Taiwan. Materials and Methods: Enrolled in this study were 80 ASD children (49 males and 31 females; 2–16 years old) followed up at Taipei MacKay Memorial Hospital between January 2010 and December 2020. The genomic DNA extracted from blood samples was analyzed by array-CGH via the Affymetrix GeneChip Genome-Wide Human single nucleotide polymorphism (SNP) and NimbleGen International Standards for Cytogenomic Arrays (ISCA) Plus Cytogenetic Arrays. The CNVs were classified into five groups: pathogenic (pathologic variant), likely pathogenic (potential pathologic variant), likely benign (potential normal genomic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance), according to the American College of Medical Genetics (ACMG) guidelines. Results: We identified 47 CNVs, 31 of which in 27 patients were clinically significant. The overall diagnostic yield was 33.8%. The most frequently clinically significant CNV was 15q11.2 deletion, which was present in 4 (5.0%) patients. Conclusions: In this study, a satisfactory diagnostic yield of array-CGH was demonstrated in a Taiwanese ASD patient cohort, supporting the clinical usefulness of array-CGH as the first-line testing of ASD in Taiwan.

Wiedemann–Steiner syndrome (WSS) is a rare genetic disorder. Patients with WSS have characteristics of growth retardation, facial dysmorphism, hypertrichosis cubiti (HC), and neurodevelopmental delays. WSS is in an autosomal dominant inherited pattern caused by a mutation of the KMT2A gene (NM_001197104.2). In this article, we discuss a 5-year-old boy who has mild intellectual disability (ID), hypotonia, HC, hypertrichosis on the back, dysmorphic facies, psychomotor retardation, and growth delay. Trio-based whole-exome sequencing (trio-WES) was carried out on this patient and his parents, confirming the variants with Sanger sequencing. Trio-WES showed a de novo mutation of the KMT2A gene (NM_001197104.2: c.4696G>A, p.Gly1566Arg). On the basis of the clinical features and the results of the WES, WSS was diagnosed. Therefore, medical professionals should consider a diagnosis of WSS if patients have growth retardation and development delay as well as hirsutism, particularly HC.

Mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases (LSDs) caused by an inherited gene defect. MPS patients can remain undetected unless the initial signs or symptoms have been identified. Newborn screening (NBS) programs for MPSs have been implemented in Taiwan since 2015, and more than 48.5% of confirmed cases of MPS have since been referred from these NBS programs. The purpose of this study was to report the current status of NBS for MPSs in Taiwan and update the gold standard criteria required to make a confirmative diagnosis of MPS, which requires the presence of the following three laboratory findings: (1) elevation of individual urinary glycosaminoglycan (GAG)-derived disaccharides detected by MS/MS-based assay; (2) deficient activity of a particular leukocyte enzyme by fluorometric assay; and (3) verification of heterogeneous or homogeneous variants by Sanger sequencing or next generation sequencing. Up to 30 April 2021, 599,962 newborn babies have been screened through the NBS programs for MPS type I, II, VI, and IVA, and a total of 255 infants have been referred to MacKay Memorial Hospital for a confirmatory diagnosis. Of these infants, four cases were confirmed to have MPS I, nine cases MPS II, and three cases MPS IVA, with prevalence rates of 0.67, 2.92, and 4.13 per 100,000 live births, respectively. Intensive long-term regular physical and laboratory examinations for asymptomatic infants with confirmed MPS or with highly suspected MPS can enhance the ability to administer ERT in a timely fashion.

Menkes disease is a rare neurodegenerative disorder caused by mutations in ATP7A gene. Deficiency in copper-dependent enzymes results in the unique kinky hair appearance, neurodegeneration, developmental delay, seizures, failure to thrive and other connective tissue or organ abnormalities. Other than biochemical tests, DNA-based diagnosis is now playing an important role. More than two hundred mutations in ATP7A gene were identified. Early copper supplementation can help improve neurological symptoms, but not non-neurological problems. Further molecular studies are needed to identify additional mutation types and to understand the mechanism of pathogenesis. This may help in discovering the possible treatment measures to cure the disease. We present a case with the clinical features and biochemical findings, abnormal brain magnetic resonance imaging as well as the effects of treatment with copper-histidine. Direct sequencing of ATP7A gene revealed a de novo point mutation which resulted in an early stop codon with truncated protein.

Infantile hypertrophic pyloric stenosis (IHPS) is a common disease in infancy. Pyloromyotomy is universally considered the treatment for IHPS; however, oral or intravenous atropine has been reappraised for the treatment of IHPS in the past 20 years. We investigated the efficacy of atropine in the medical management of IHPS by using meta-analysis and investigated the sonographic changes of the pyloric canal, as well as the efficacy and adverse effects of atropine. Methods: Information was retrieved from PubMed, Ovid, and MEDLINE. The efficacy and adverse effects of atropine treatment for IHPS were reviewed using the standard process of meta-analysis. Results: Eleven articles were obtained. Five reports showed that 77 of 110 (70%) infants who were administered oral atropine benefitted by the induced remission of IHPS. Six reports showed that 288 of 345 (83.5%) patients who were treated initially with intravenous atropine then changed to oral atropine showed beneficial effects and had no serious side effects. Time to pyloric muscle normalization ranged from 5 weeks to 15 months. Conclusion: The study results indicate that atropine is a possible alternative treatment for IHPS, particularly in infants with major concurrent disease, and is safe without obvious side effects.

The goal of modern neonatal care of extremely preterm infants is to reduce mortality and long-term neurological impairments. Preterm infants frequently experience cerebral intraventricular or pulmonary hemorrhage, which usually occurs within 72 hours after birth and can lead to long-term neurological sequelae and mortality. These serious hemorrhagic complications are closely related to perinatal hemodynamic changes, including an increase in the afterload on the left ventricle of the heart after the infant is separated from the placenta, and an increased preload from a left-to-right shunt caused by a hemodynamically significant patent ductus arteriosus (PDA). The left ventricle of a preterm myocardium has limited ability to respond to such an increase in afterload and preload, and this can result in cardiac dysfunction and hemodynamic deterioration. We suggest that delayed umbilical cord clamping or umbilical cord milking to maintain optimal blood pressure and systemic blood flow (SBF), careful assessment to keep the afterload at an acceptable level, and a strategy of early targeted treatment of significant PDA to improve perfusion during this critical time period may reduce or prevent these serious complications in preterm infants.

Abstract Background Information on functional strengths and weaknesses of mucopolysaccharidosis (MPS) patients is important for early intervention programs and enzyme replacement therapy (ERT). Methods We used the Functional Independence Measure for Children (WeeFIM) questionnaire to assess the functional skills of 63 Taiwanese MPS patients (median age, 13 years 3 months; range, 3–20 years) from January 2012 to December 2018. Results Mean total WeeFIM score was 75.4 of a potential score of 126. Mean total WeeFIM scores of each type (MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI) were 103.8, 76.2, 41.6, 92.2, and 113.6, respectively. Mean scores for self‐care, mobility, and cognition domains were 30 (maximum 56), 23 (maximum 35), and 22 (maximum 35), respectively. MPS type IIIB patients had the lowest scores in self‐care, mobility, cognition, and total domains compared to other types of MPS. All patients with ERT in MPS I, II, and IVA had higher scores in self‐care and mobility domains than patients without ERT. Most patients required assistance for self‐care skills, especially in grooming and bathing. Conclusion MPS patients require support and supervision in self‐care tasks. For cognition tasks, MPS IIIB patients also require help. This questionnaire is useful to identify the strengths and limitations of MPS patients.

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.

Background: Information regarding the long-term outcome of enzyme replacement therapy (ERT) with recombinant human N-acetylgalactosamine 4-sulfatase (rhASB, galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.) for Taiwanese patients with mucopolysaccharidosis (MPS) VI is limited. Methods: Nine Taiwanese patients with MPS VI (4 males and 5 females; age range, 1.4 to 21.1 years) treated with weekly intravenous infusions of galsulfase (1.0 mg/kg) in 5 medical centers in Taiwan were reviewed. A set of biochemical and clinical assessments were evaluated annually. Results: After 6.2 to 11.2 years of galsulfase treatment, 6 patients experienced improvement over baseline in the 6-minute walk test by a mean of 150 m (59% change over time), and 3 patients also increased the 3-minute stair climb test by a mean of 60 steps (46%). In a manual dexterity test, 3 patients decreased the time required to pick up 10 coins and put the coins into a cup by 15 s (33%). Shoulder range of motion in all 9 patients improved, and Joint Pain and Stiffness Questionnaire scores improved by 0.42 points (21%). Four patients showed improved pulmonary function. Five patients had positive effects on cardiac-wall diameters. Four patients had improved cardiac diastolic function. Liver and spleen sizes as measured by abdominal ultrasonography remained the same or decreased in all 9 patients. However, the severity degree of valvular stenosis or regurgitation did not show improvement despite ERT. A mean overall 69% decrease in urinary glycosaminoglycan (GAG) excretion indicated a satisfactory biomarker response. Conclusions: Long-term ERT was beneficial and safe for Taiwanese patients with MPS VI. This treatment reduced urinary GAG and had positive effects on a wide range of clinical functional assessments including endurance, mobility, joint function, pulmonary function, liver and spleen size, cardiac hypertrophy and diastolic dysfunction.

Mucopolysaccharidosis type II (MPS II) is an X-linked disorder resulting from a deficiency in iduronate 2-sulfatase (IDS), which is reported to be caused by gene mutations in the iduronate 2-sulfatase (IDS) gene. Many IDS mutation sites have not yet had their causal relationship with MPS II characterized. We employed a gain-of-function strategy whereby we microinjected different mutated zebrafish ids (z-ids) mRNAs corresponded to human IDS gene into zebrafish embryos, and then measured their total IDS enzymatic activity and observed the occurrence of defective phenotypes during embryonic development. We examined three known mutation sites for human IDS genes (h-IDS) associated with MPS II symptoms, including h-IDS-P86L, -S333L and -R468W, which corresponded to z-ids-P80L, -S327L and -R454W. When these three mutated z-ids mRNAs were overexpressed in zebrafish embryos, the IDS enzymatic activity of the total proteins extracted from the injected embryos was not increased compared with the endogenous IDS of the untreated embryos, which suggests that the IDS enzymatic activity of these three mutated z-ids was totally lost, as expected. Additionally, we observed defective phenotypes in these injected embryos, resulting from the failed IDS enzyme breakdown, which, in turn, has a dominant negative effect on the endogenous wild-type IDS function. These phenotypes were similar to the clinical symptoms observed in MPS II pathogenesis. We further studied six uncharacterized IDS mutation sites as identified by the Taiwanese MPS newborn screening programs. We propose a novel IDS enzyme activity assay combined with phenotypic observation in zebrafish embryos, as an alternative platform for quickly providing a valuable index for preliminarily assessment of any identified IDS point mutation gene that has not yet been characterized, in the context of its role in MPS II development.

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.

We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.

Necrotizing enterocolitis (NEC) is still one of the most catastrophic intestinal emergencies in preterm very low-birth weight infants. Primary prevention of NEC should be the priority, since NEC frequently progresses from nonspecific signs, to extensive necrosis within a matter of hours with medical or surgical treatment, making successful treatment and secondary prevention difficult to achieve. Currently available strategies for primary prevention of NEC include antenatal glucocorticosteroids, breast milk feeding, cautious feeding strategy, fluid restriction and probiotics. Nonetheless, based on current research evidence, mixed flora probiotics, and/or breast milk feeding, would appear to be the most effective feasible methods in the prevention of NEC at present.

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 (

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.

This study investigated the use of bioelectrical impedance analysis (BIA) as a means of assessing body composition in patients with Prader-Willi syndrome (PWS). Segmental, multifrequency BIA was performed on 30 patients with PWS (16 males and 14 females; mean age: 8.1 ± 3.9 years; age range: 2.9–19.6 years) using eight tactile electrodes. No patient had received growth hormone treatment prior to baseline measurements. Standard deviation scores for height, weight, and body mass index were –0.96 ± 1.29, 2.28 ± 2.66, and 3.14 ± 2.74, respectively. Percentages of body fat, total body water, and soft lean mass were 45.9 ± 10.8%, 36.6 ± 7.3%, and 49.9 ± 9.9%, respectively. Body fat percentage was positively correlated with the body mass index standard deviation score (r = 0.665, p

Most premature babies are discharged with low body weight. Creamatocrit represents the lipid concentration of breast milk. We expected the creamatocrit technique could be applied in the nutrition plan for premature infants who were exclusively fed by human milk. Methods: Breast milk samples were obtained from the mothers whose babies were admitted to the neonatal intensive care unit or sick baby room. The breast milk provider was enrolled under the criteria of stable breast milk expression 2 weeks after having given birth. Breast milk was collected for 7 consequent days. Creamatocrit technique and calorie analysis were performed on the processed breast milk samples. Results: Fourteen pairs of mothers and infants were enrolled in our study. The median gestational age and birth weight were 29 weeks (27–36 weeks) and 1393 g (680–3050 g), respectively. The mean calorie and creamatocrit values for all the 98 breast milk samples were 0.67 kcal/mL and 5.98%, respectively. The linear correlation between creamatocrit value and laboratory-measured calories was found to be calories (kcal/mL)=0.39+0.048×creamatocrit (%) (p

Osteogenesis imperfecta (OI) (MIM 166200, 166210, 259420 and 166220) is a congenital disorder characterized by increased bone fragility and low bone mass. Information regarding the clinical features of this genetic disorder is lacking in Taiwan. This study aimed to characterize the clinical features of OI patients in Taiwan to establish a practical correlation for distinguishing different clinical subtypes of the disorder. Methods: A review of medical records identified 48 patients with OI (33 female and 15 male; age range, 2 months to 53 years) from January 1996 to June 2008. Diagnosis and classification, using the classification system outlined by Sillence et al, were based on clinical and radiological characteristics. We also analyzed the clinical presentation, physical examination and bone mineral density (BMD) among the different subtypes of OI. Results: Retrospective analysis of the medical records revealed that 48 OI patients could be classified into types I (n = 19), III (n = 10), and IV (n = 19). There were statistically significant differences between these three types in terms of height, weight, BMD, dentinogenesis imperfecta, bone deformity, scoliosis, walking ability, annual fracture rate, and family history. However, no significant differences were noted for blue sclera (p = 0.075) and hearing loss (p = 0.832). Conclusion: Nine of the 11 clinical features examined—height, weight, BMD, dentinogenesis imperfecta, bone deformity, scoliosis, walking ability, fracture rate, and family history—were significantly different among the three types of OI patients. This finding may be of help in evaluating patients and establishing their prognosis.

We report a male, preterm newborn infant with X-linked myotubular myopathy, the most severe type of the disease. He presented at birth with generalized hypotonia, difficulty in swallowing, and respiratory distress with frequent episodes of atelectasis. The infant had a long thin face, generalized hypotonia, and arachnodactyly. Diagnosis was based on fetal history, muscle histopathology, electron microscopy and a genetic study. A base pair change was detected in exon 11 of the MTM1 gene: c.1160C > A, which caused an amino acid change, p.S387Y. The father's gene was normal but the mother had the same mutation as her son and was thus a carrier.

Information on the long-term efficacy of intravenous pamidronate therapy in Asian patients with osteogenesis imperfecta (OI) is limited. We report our experience using pamidronate in Taiwanese patients with OI. Methods: Twenty-six patients with type I, III, or IV OI (eight males and 18 females; age range at last follow-up, 2.9-39.2 years) who received (or were currently receiving) intravenous pamidronate treatment (30 mg/m2/dose, every month) were retrospectively analyzed. Patients were followed for 1.0-7.3 years over the study period from February 2000 to October 2007. Results: The mean standard deviation score (SDS) for bone mineral density (BMD) had increased significantly from −4.72 to −3.37 (p < 0.005) after 1 year of treatment. In 16 patients evaluated after 4 years and eight after 6 years, the mean SDS continued to improve, to −2.69 (p < 0.001) and −1.54 (p < 0.005), respectively. The fracture rate decreased significantly (from 2.8 ± 1.1 to 0.6 ± 0.6, p < 0.001), and nine patients (35%) had no fractures while receiving treatment. The response to pamidronate was significantly better in patients with poorer initial BMD SDS (1 year: r = −0.71, p < 0.01; 4 years: r = −0.81, p < 0.01). Conclusion: This retrospective study suggests that Taiwanese patients with OI can benefit from pamidronate treatment, leading to a reduced incidence of fractures and increased BMD, especially in patients with poor baseline BMD.