RESUMO
Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.
Assuntos
Transtornos da Impressão Genômica , Síndrome de Silver-Russell , Recém-Nascido , Feminino , Gravidez , Humanos , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Síndrome de Silver-Russell/patologia , Metilação de DNA/genética , Fenótipo , Dissomia Uniparental/genéticaRESUMO
Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.
Assuntos
Síndrome de DiGeorge , Cardiopatias Congênitas , Hipocalcemia , Tetralogia de Fallot , Humanos , Feminino , Masculino , Síndrome de DiGeorge/genética , Síndrome de DiGeorge/diagnóstico , Tetralogia de Fallot/genética , Hipocalcemia/genética , Hibridização in Situ Fluorescente , Taiwan/epidemiologia , Estudos Transversais , Hibridização Genômica Comparativa , Cardiopatias Congênitas/genética , Sistema Imunitário , Deleção CromossômicaRESUMO
Background: Fabry disease is an inherited lysosomal storage disease affecting multiple organs with complications, including cardiomyopathy such as left ventricular hypertrophy (LVH). Enzyme replacement therapy (ERT) has been the main treatment for Fabry patients since 2001. However, the indications of ERT are not clearly defined. We performed a meta-analysis according to previous studies to review the benefit of ERT for LVH improvement in Fabry patients. Methods: We performed a literature search from the National Center for Biotechnology Information (NCBI) and PubMed database without restriction of years for systematic review purposes. We performed a systematic review of clinical cohort studies and trials using a pooled analysis of proportions. We calculated the pooled proportions and the confidence intervals (CI) for left ventricular mass index (LVMI) for both ERT treatment and ERT treatment-naïve groups. The results for before ERT treatment and after ERT treatment are also investigated. Results: A total of 5 cohort studies and 2 randomized controlled trials (RCTs), involving a total of 552 participants (267 on ERT treatment versus 285 on naïve treatment), met the inclusion criteria. The pooled proportions analysis showed that the difference in means of LVMI between the ERT treatment group and the ERT treatment-naïve group was -0.149 [95% CI: -0.431, 0.132]. Effect differences favored the ERT treatment group over the ERT treatment-naïve group (p = 0.034). Another analysis included 3 cohort studies and 1 RCT with 442 participants (228 on before ERT and 214 on 4 years after ERT). The pooled proportions analysis showed that the difference in means of LVMI between the before ERT treatment group and the after ERT treatment group was -0.448 [95% CI: -0.787, -0.108]. It favored the 4 years after ERT group over the before ERT group (p = 0.037). Conclusions: Based on the currently available data, our meta-analysis showed that there are beneficial effects on LVH improvement with ERT in Fabry disease patients. It is better to start ERT as soon as we have diagnoses in female carriers and atypically affected males. Further research is needed to investigate the role of ERT in LVH improvement.
Assuntos
Terapia de Reposição de Enzimas , Doença de Fabry/complicações , Doença de Fabry/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Feminino , Humanos , MasculinoRESUMO
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 ß-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.
Assuntos
Mucopolissacaridose VII , Pré-Escolar , Feminino , Humanos , Mucopolissacaridose VII/diagnóstico , Mucopolissacaridose VII/genética , Mucopolissacaridose VII/terapia , Gravidez , Radiografia , Amplitude de Movimento Articular , TaiwanRESUMO
Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.
Assuntos
Mucopolissacaridoses , Mucopolissacaridose II , Mucopolissacaridose I , Dissacarídeos , Glicosaminoglicanos/genética , Humanos , Lactente , Recém-Nascido , Mucopolissacaridoses/diagnóstico , Mucopolissacaridoses/genética , Espectrometria de Massas em Tandem/métodosRESUMO
Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. We collected, analyzed, and uniformly summarized all published GALNS gene variants, thus updating the previous mutation review (published in 2014). In addition, new variants were communicated by seven reference laboratories in Europe, the Middle East, Latin America, Asia, and the United States. All data were analyzed to determine common alleles, geographic distribution, level of homozygosity, and genotype-phenotype correlation. Moreover, variants were classified according to their pathogenicity as suggested by ACMG. Including those previously published, we assembled 446 unique variants, among which 68 were novel, from 1190 subjects (including newborn screening positive subjects). Variants' distribution was missense (65.0%), followed by nonsense (8.1%), splicing (7.2%), small frameshift deletions(del)/insertions(ins) (7.0%), intronic (4.0%), and large del/ins and complex rearrangements (3.8%). Half (50.4%) of the subjects were homozygous, 37.1% were compound heterozygous, and 10.7% had only one variant detected. The novel variants underwent in silico analysis to evaluate their pathogenicity. All variants were submitted to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) to make them publicly available. Mutation updates are essential for the correct molecular diagnoses, genetic counseling, prenatal and preimplantation diagnosis, and disease management.
Assuntos
Condroitina Sulfatases/genética , Mucopolissacaridose IV/genética , Mutação , Estudos de Associação Genética , HumanosRESUMO
Background: Osteogenesis imperfecta (OI) is a rare disease characterized by increased bone fragility and susceptibility for fractures. Only few studies have compared the management for femoral fractures in children with OI. Nevertheless, no cohort studies have described the treatment for femoral fractures in adults with OI in Taiwan. This study aimed to investigate and compare the incidence of union and non-union femoral fractures and the best treatment options to avoid non-union fractures. Methods: We enrolled 72 patients with OI who were older than 18 years at MacKay Memorial Hospital between January 2010 and December 2018. Femoral fracture incidence, non-union rate, and treatment modality were analyzed. Results: Of 72 patients with OI, 11 patients had femoral fractures and 4 patients of them had >1 femoral fracture. The incidence for all types of femoral fractures was 651 fractures per 100,000 person-years annually. In 15 total fractures, 4 fractures resulted in non-union, and patients with type 4 OI mostly had shaft fractures. The best outcomes for non-union shaft fracture is achieved by surgical treatment. Conclusion: Adults with OI tended to develop femoral fractures and non-unions. Adults with type 4 OI were particularly at high risk for non-unions in shaft fractures with conservative treatment.
Assuntos
Fraturas do Fêmur/epidemiologia , Osteogênese Imperfeita/complicações , Adulto , Conservadores da Densidade Óssea/uso terapêutico , Tratamento Conservador/métodos , Feminino , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/terapia , Fixação de Fratura/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Taiwan/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
Background: Mucopolysaccharidoses (MPSs) are lysosomal storage disorders wherein glycosaminoglycans accumulate because the enzymes that degrade them are insufficient. The earliest symptoms, which are the main reasons for seeking consultation, are otorhinolaryngological and commonly occur in MPS I, II, IV, and VI. This retrospective study aimed to determine the occurrence of otorhinolaryngological manifestations in MPS patients in Taiwan and to analyze the prognosis of surgical intervention, including its effect on symptoms. Methods: We reviewed 42 patients (30 males and 12 females), with a median age of 20.5 years, who had MPS (16.7% type I, 35.7% type II, 19.0% type IIIB, 21.4% type IVA, and 7.2% type VI). The following otorhinolaryngological manifestations were collected: annual number of upper respiratory tract infections (URTIs) and otitis media with effusion (OME) episodes, adenoid size, tonsillar size, and apnea-hypopnea index (AHI). Results: Among 42 patients, we found recurrent otitis media in 42.9% of the patients, hearing loss in 83.3% (mixed: 52.4%, conductive: 21.4%, and sensorineural: 9.5%), frequent URTIs in 47.6%, and obstructive sleep apnea syndrome in 35.7%. Moreover, 76% of the patients underwent ear, nose, and throat (ENT) surgery, including adenoidectomy, tonsillectomy, tympanostomy with ventilation tube insertion, tracheotomy, and supraglottoplasty. Conclusions: MPS patients had a high incidence of ENT problems. ENT surgery reduced the severity of hearing loss, degree of symptoms related to upper airway obstruction, and severity of respiratory tract and otological infections of patients with MPS.
Assuntos
Mucopolissacaridoses/complicações , Otorrinolaringopatias/epidemiologia , Procedimentos Cirúrgicos Otorrinolaringológicos/estatística & dados numéricos , Feminino , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Humanos , Masculino , Otite Média com Derrame/epidemiologia , Otite Média com Derrame/etiologia , Otorrinolaringopatias/etiologia , Otorrinolaringopatias/cirurgia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/etiologia , Taiwan/epidemiologia , Adulto JovemRESUMO
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.
Assuntos
Transtorno do Espectro Autista , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Criança , Pré-Escolar , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , TaiwanRESUMO
RASopathies are developmental diseases caused by mutations in rat sarcoma-mitogen-activated protein kinase pathway genes. These disorders, such as Noonan syndrome (NS) and NS-related disorders (NSRD), including cardio-facio-cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML; also known as LEOPARD syndrome), have a similar systemic phenotype. A wide spectrum of congenital heart disease and hypertrophic cardiomyopathy (HCMP) can exhibit major associated characteristics. A retrospective study was conducted at the Mackay Memorial Hospital, National Taiwan University Hospital, Buddhist Tzu-Chi General Hospital, Chang-Gung Memorial Hospital, Taichung Veterans General Hospital, and Chung Shan Medical University Hospital from January 2007 to December 2018. We reviewed the clinical records of 76 patients with a confirmed molecular diagnosis of RASopathies, including NS, CS, CFC syndrome, and NSML. We evaluated the demographic data and medical records with clinical phenotypes of cardiac structural anomalies using cross-sectional and color Doppler echocardiography, electrocardiographic findings, and follow-up data. A total of 47 (61.8%) patients had cardiac abnormalities. The prevalence of cardiac lesions according to each syndrome was 62.7, 50.0, 60.0, and 66.7% in patients with NS, CFC syndrome, CS, and NSML, respectively. An atrial septal defect was usually combined with other cardiac abnormalities, such as pulmonary stenosis (PS), HCMP, ventricular septal defect, or patent ductus arteriosus. Patients with NS most commonly showed PS. In patients with NSRD and cardiac abnormalities, HCMP (29.4%) was the most commonly observed cardiac lesion. PTPN11 was also the most frequently detected mutation in patients with NS and NSRD. Cardiac abnormalities were the most common symptoms observed in patients with RASopathies at the time of their first hospital visit. Performing precise analyses of genotype-cardiac phenotype correlations in a larger cohort will help us accurately diagnose RASopathy as soon as possible.
Assuntos
Deficiências do Desenvolvimento/genética , Cardiopatias Congênitas/genética , Síndrome de Noonan/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/fisiopatologia , Síndrome de Costello/genética , Síndrome de Costello/fisiopatologia , Estudos Transversais , Deficiências do Desenvolvimento/classificação , Deficiências do Desenvolvimento/patologia , Displasia Ectodérmica/genética , Displasia Ectodérmica/fisiopatologia , Fácies , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/fisiopatologia , Feminino , Cardiopatias Congênitas/fisiopatologia , Comunicação Interatrial/genética , Comunicação Interatrial/fisiopatologia , Humanos , Síndrome LEOPARD/genética , Síndrome LEOPARD/fisiopatologia , Masculino , Síndrome de Noonan/fisiopatologia , Estudos Retrospectivos , Proteínas ras/genéticaRESUMO
OBJECTIVE: To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan. STUDY DESIGN: More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by tandem mass spectrometry from dried blood spot punches. Genotypes were obtained when a second newborn screening specimen again had a decreased enzyme activity. Additional clinical evaluation was then initiated based on enzyme activity and/or genotype. RESULTS: Molecular genetic analysis for cases with low enzyme activity revealed 5 newborns with pathogenic alpha-L-iduronidase mutations, 3 newborns with pathogenic iduronate-2-sulfatase mutations, and 1 newborn was a carrier of an arylsulfatase B mutation. Several variants of unknown pathogenic significance were also identified, most likely causing pseudodeficiency. CONCLUSIONS: The highly robust tandem mass spectrometry-based enzyme assays for MPS-I, MPS-II, and MPS-VI allow for high-throughput newborn screening for these lysosomal storage disorders. Optimized cutoff values combined with second tier testing could largely eliminate false-positive results. Accordingly, newborn screening for these lysosomal storage disorders is possible.
Assuntos
Mucopolissacaridose II/diagnóstico , Mucopolissacaridose IV/diagnóstico , Mucopolissacaridose I/diagnóstico , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem/métodos , Teste em Amostras de Sangue Seco/métodos , Testes Genéticos/métodos , Humanos , Recém-Nascido , Morbidade/tendências , Mucopolissacaridose I/epidemiologia , Mucopolissacaridose I/genética , Mucopolissacaridose II/epidemiologia , Mucopolissacaridose II/genética , Mucopolissacaridose IV/epidemiologia , Mucopolissacaridose IV/genética , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
Hunter syndrome (mucopolysaccharidosis II; MPS II) is caused by a defect of the iduronate-2-sulfatase (IDS) gene. Few studies have reported integrated mutation data of Taiwanese MPS II phenotypes. In this study, we summarized genotype and phenotype correlations of confirmed MPS II patients and asymptomatic MPS II infants in Taiwan. Regular polymerase chain reaction and DNA sequencing were used to identify genetic abnormalities of 191 cases, including 51 unrelated patients with confirmed MPS II and 140 asymptomatic infants. IDS activity was analyzed in individual novel IDS variants using in vitro expression studies. Nineteen novel mutations were identified, in which the percentages of IDS activity of the novel missense mutations c.137A>C, c.311A>T, c.454A>C, c.797C>G, c.817C>T, c.998C>T, c.1106C>G, c.1400C>T, c.1402C>T, and c.1403G>A were significantly decreased (p < 0.001), c.254C>T and c.1025A>G were moderately decreased (p < 0.01), and c.851C>T was slightly decreased (p < 0.05) comparing with normal enzyme activity. The activities of the other six missense mutations were reduced but were insignificant. The results of genomic studies and their phenotypes were highly correlated. A greater understanding of the positive correlations may help to prevent the irreversible manifestations of Hunter syndrome, particularly in infants suspected of having asymptomatic MPS II. In addition, urinary glycosaminoglycan assay is important to diagnose Hunter syndrome since gene mutations are not definitive (could be non-pathogenic).
Assuntos
Glicoproteínas/metabolismo , Mucopolissacaridose II , Mutação de Sentido Incorreto , Povo Asiático , Feminino , Glicoproteínas/genética , Humanos , Lactente , Masculino , Mucopolissacaridose II/enzimologia , Mucopolissacaridose II/genética , Mucopolissacaridose II/urina , Análise de Sequência de DNA , TaiwanRESUMO
Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) has a variable age of onset and variable rate of progression. However, information regarding the natural history of this disorder in Asian populations is limited. A retrospective analysis was carried out for 28 patients with MPS III (types IIIA [n = 3], IIIB [n = 23], and IIIC [n = 2]; 15 males and 13 females; median age, 8.2 years; age range, 2.7-26.5 years) seen in six medical centers in Taiwan from January 1996 through October 2017. The median age at confirmed diagnosis was 4.6 years. The most common initial symptom was speech delay (75%), followed by hirsutism (64%) and hyperactivity (54%). Both z scores for height and weight were negatively correlated with age (r = -.693 and -0.718, respectively; p < .01). The most prevalent clinical manifestations were speech delay (100%) and intellectual disability (100%), followed by hirsutism (93%), hyperactivity (79%), coarse facial features (68%), sleep disorders (61%), and hepatosplenomegaly (61%). Ten patients (36%) had epilepsy, and the median age at the first seizure was 11 years. Thirteen patients (46%) experienced at least one surgical procedure. At the time of the present study, 7 of the 28 patients had passed away at the median age of 13.0 years. Molecular studies showed an allelic heterogeneity without clear genotype and phenotype correlations. MPS IIIB is the most frequent subtype among MPS III in the Taiwanese population. An understanding of the natural history of MPS III may allow early diagnosis and timely management of the disease facilitating better treatment outcomes.
Assuntos
Mucopolissacaridose III/diagnóstico , Mucopolissacaridose III/etiologia , Acetilglucosaminidase/genética , Acetilglucosaminidase/metabolismo , Adolescente , Adulto , Biomarcadores , Criança , Pré-Escolar , Análise Mutacional de DNA , Eletroencefalografia , Ativação Enzimática , Feminino , Estudos de Associação Genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Mucopolissacaridose III/metabolismo , Mucopolissacaridose III/mortalidade , Imagem Multimodal/métodos , Mutação , Fenótipo , Estudos Retrospectivos , Avaliação de Sintomas , Taiwan , Adulto JovemRESUMO
Prader-Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty-five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self-care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem-solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self-care tasks.
Assuntos
Atividades Cotidianas , Cognição/fisiologia , Síndrome de Prader-Willi/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Prader-Willi/fisiopatologia , Autocuidado , Inquéritos e Questionários , Taiwan , Adulto JovemRESUMO
Human milk is considered optimal nutrition for newborn infants, especially preterm infants, and it can lessen morbidity in this population. Human milk feeding at hospital discharge may encourage breastfeeding at home. This study evaluated the incidence and predictive factors of human milk feeding of preterm infants at discharge. It included all preterm infants with gestational age of less than 37 weeks who were admitted to the Mackay Memorial Hospital in Taiwan from January to December 2010 who survived to discharge. Infants were classified into a human milk group or a formula milk group. Gestational age, birth weight, length of hospital stay, maternal age, maternal educational status, and morbidity of prematurity were compared between the groups. Of the 290 preterm infants, 153 (52.8%) were being fed human milk at hospital discharge. Compared with the formula milk group, the human milk group had lower birth weights, younger gestational age, higher rates of ventilator use, and longer hospital stays. These differences were not statistically significant for very low-birth-weight (birth weight of <1500 g) infants (n = 66). Multivariate analysis indicated that 2 factors, longer hospital stay and neonatal intensive care unit admission, were associated with human milk feeding at hospital discharge. These findings highlight the need for encouraging and helping all mothers, even those with relatively mature and healthy infants, to provide human milk for their infants.
Assuntos
Aleitamento Materno , Fórmulas Infantis , Doenças do Prematuro/epidemiologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Leite Humano , Aleitamento Materno/métodos , Aleitamento Materno/estatística & dados numéricos , Escolaridade , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Recém-Nascido Prematuro/fisiologia , Masculino , Avaliação das Necessidades , Alta do Paciente/normas , Melhoria de Qualidade , Taiwan/epidemiologiaRESUMO
BACKGROUND: Urinary tract infections are a common iatrogenic infection in healthcare institutions. Catheter-associated urinary tract infections (CAUTIs) may result in sepsis, prolonged hospitalization, additional hospital costs, and mortality. PURPOSE: The study examined the efficacy of an indicator-based reminder of catheter removal in decreasing CAUTIs among patients in the general medical ward. METHODS: A two-group, quasi-experimental design was used. The intervention strategies included daily implementation of the indicator-based reminder procedure and standardized Foley care and a teaching program for all staff nurses. All patients who received Foley during hospitalization were included, with the exception of those with CAUTI at admission. Seventy-five patients were enrolled from five wards in a medical center, with 33 assigned to the control group and 42 assigned to the experimental group. RESULTS: CAUTIs were diagnosed in 7 participants (16.7%) in the experimental group and 15 participants (45.5%) in the control group. The differences were statistically significant (p = .014). The mean number of Foley days was 14.73% less in the experimental group, with 11.0 for the experimental group and 12.9 for the control group. The incidence density of CAUTIs was 15.2% for the experimental group and 35.3% for the control group. CONCLUSIONS: The present study supports that an indicator-based reminder of catheter removal decreases the incidence rate and incidence density of CAUTIs. Medical personnel in the general medical ward may use this reminder to detect unnecessary indwelling of urinary catheters and to remove Foley catheters as early as feasible in order to prevent CAUTIs.
Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Remoção de Dispositivo/métodos , Sistemas de Alerta , Cateterismo Urinário/efeitos adversos , Infecções Urinárias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: While enzyme replacement therapy (ERT) has been shown to improve endurance and joint mobility for patients with mucopolysaccharidoses (MPS) I, II, IVA and VI, the impact of ERT on cardiac abnormalities remains uncertain. METHODS: Medical records and echocardiograms of 28 Taiwanese MPS patients (9 with MPS I, 7 with MPS II, 7 with MPS IVA, and 5 with MPS VI) treated with ERT for 1-10.8years were retrospectively reviewed. RESULTS: At start of ERT, z scores>2 were identified in 46% and 75% for left ventricular mass index (LVMI) and interventricular septum thickness in diastole (IVSd) in these patients, respectively. Twenty-four patients (86%) had valvular heart disease. After ERT, the mean IVSd z score of all patients decreased significantly from 3.87 to 2.57 (p=0.016). For 11 patients starting ERT before 12years of age, z scores for both LVMI and IVSd decreased significantly (p<0.01) after ERT. However, the condition of valve regurgitation or stenosis did not show improvement despite ERT. CONCLUSIONS: ERT was shown to be an effective therapy for reducing cardiac hypertrophy, with best results seen when ERT was started at an early age. ERT, however, had little impact on valvular heart disease.
Assuntos
Terapia de Reposição de Enzimas , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Coração/fisiopatologia , Mucopolissacaridoses/complicações , Mucopolissacaridoses/terapia , Miocárdio/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Mucopolissacaridoses/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis that results from abnormal expression or function of imprinted genes of chromosome 11p15.5. METHODS: Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling. RESULTS: Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups-clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively. CONCLUSIONS: The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.
Assuntos
Síndrome de Beckwith-Wiedemann/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Impressão Genômica , RNA Longo não Codificante/genética , Adolescente , Adulto , Síndrome de Beckwith-Wiedemann/fisiopatologia , Criança , Pré-Escolar , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Adulto JovemRESUMO
AIM: Information regarding the functional strengths and weaknesses of children with Down syndrome is important for early intervention programmes and for agencies providing family support and educational services. METHOD: This study used the Functional Independence Measure for Children (WeeFIM) questionnaire for the parents or caregivers of 166 Taiwanese children (101 males and 65 females; median age 12y 7mo; range 3y 2mo-19y 1mo) with Down syndrome to assess their functional skills. RESULTS: Out of a potential score of 126, the mean total WeeFIM score was 101.2. There was no statistically significant difference between the scores from the male and female participants (100.4 [SD 21.4] vs 102.4 [SD 24.7]; p>0.05). The mean scores for three domains (self-care, mobility, and cognition) were 45, 33, and 23 respectively (maximum of 56, 35, and 35 respectively). Performance was strongest in the mobility domain and weakest in the cognition domain. The total WeeFIM scores and 18 subscores for the three domains all positively correlated with age (p<0.05). INTERPRETATION: For children with Down syndrome, some support and supervision is required for cognition and self-care tasks. The WeeFIM questionnaire may be useful for identifying the strengths and limitations of children with developmental disabilities and their families.