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OBJECTIVE: To quantitatively measure femoral bone marrow involvement in patients with Gaucher disease (GD) by using fat fraction (FF) derived from the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) technique. METHODS: Bilateral femora of 23 patients with type 1 GD receiving low-dose imiglucerase treatment were prospectively scanned using structural magnetic resonance imaging sequences and an IDEAL-IQ sequence. Femoral bone marrow involvement was evaluated by both semiquantification (bone marrow burden [BMB] score based on magnetic resonance imaging structural images) and quantification (FF derived from IDEAL-IQ) methods. These patients were further divided into subgroups according to whether they underwent splenectomy or had bone complications. The interreader agreement of measurements and the correlation between FF and clinical status were statistically analyzed. RESULTS: In patients with GD, both BMB and FF evaluation of femora showed good interreader concordance (intraclass correlation coefficient = 0.98 and 0.99, respectively), and FF highly correlated with BMB score ( P < 0.001). The longer the duration of disease, the lower the FF ( P = 0.026). Femoral FF was lower in subgroups with splenectomy or bone complications than those without splenectomy or bone complications (0.47 ± 0.08 vs 0.60 ± 0.15, 0.51 ± 0.10 vs 0.61 ± 0.17, respectively, both P < 0.05). CONCLUSION: Femoral FF derived from IDEAL-IQ could be used to quantify femoral bone marrow involvement in patients with GD, and low bone marrow FF may predict worse outcomes of GD patients in this small-scale study.
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Doença de Gaucher , Humanos , Doença de Gaucher/diagnóstico por imagem , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Imageamento por Ressonância Magnética/métodos , Água , Fêmur/diagnóstico por imagemRESUMO
OBJECTIVES: To study the efficacy of a low-copper diet guidance based on food exchange portions in children with hepatolenticular degeneration. METHODS: A self-controlled study was conducted from July 2021 to June 2022, including 30 children under the age of 18 who were diagnosed with hepatolenticular degeneration and poorly controlled with a low-copper diet. During the medical visit, personalized low-copper diet guidance was provided to the children and their parents using a copper-containing food exchange table and a copper food exchange chart. During home care, compliance with the low-copper diet of the children was improved by recording dietary diaries and conducting regular follow-ups. The changes in 24-hour urine copper level, liver function indicators, and the low-copper diet knowledge of the children's parents were observed before and after the intervention, with no change in the original drug treatment. RESULTS: After 8, 16, and 24 weeks of intervention, the 24-hour urine copper level decreased significantly compared to before intervention (P<0.05). When compared to 8-week intervention, the urine copper level decreased significantly after 16 and 24 weeks of intervention. The 24-hour urine copper level after 24 weeks of intervention decreased significantly compared to 16 weeks of intervention (P<0.05).After 24 weeks of intervention, the alanine aminotransferase and aspartate aminotransferase levels decreased significantly compared to before intervention (P<0.05). Additionally, in 16 of the cases (53%), alanine aminotransferase and aspartate aminotransferase returned to normal levels. Following 8 weeks of intervention, the low-copper diet knowledge of the children's parents increased significantly (P<0.05). CONCLUSIONS: A low-copper diet guidance based on food exchange portions can effectively decrease the urine copper level and improve liver function in children with hepatolenticular degeneration. Furthermore, it can increase the low-copper diet knowledge of the children's parents.
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Degeneração Hepatolenticular , Humanos , Criança , Degeneração Hepatolenticular/terapia , Alanina Transaminase , Cobre , Alimentos , Aspartato AminotransferasesRESUMO
BACKGROUND: Transient antenatal Bartter's syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. CASE PRESENTATION: We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter's syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter's syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. CONCLUSIONS: We reported the first Chinese case of transient antenatal Bartter's syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos de Neoplasias/genética , Síndrome de Bartter/genética , Doenças Fetais/genética , Mutação , Povo Asiático , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Remissão Espontânea , Fatores de TempoRESUMO
Exonic deletions and duplications within DMD are the main pathogenic variants in Duchenne and Becker muscular dystrophies (DMD/BMD). However, few studies have profiled the flanking sequences of breakpoints and the potential mechanism underlying the breakpoints in different fragile regions of DMD. In this study, 896 Chinese male probands afflicted with DMD/BMD were selected from unrelated families and analyzed using multiplex ligation-dependent probe amplification of the DMD gene, in which we identified exon deletions in 784 subjects and duplications in 112 subjects. Deletions occurred most frequently in the genomic region encompassing exons 45-55, accounting for 73% of all deletion patterns. Furthermore, to unravel the potential mechanism that induced breaks, DMD gene capture and sequencing were performed to identify the breakpoints in 37 subjects with deletions encompassing exons 45-55 of DMD; we found that DMD instability did not arise from a single cause; instead, long-sequence motifs, nonconsensus microhomologies, low-copy repeats, and microindels were embedded around the breakpoints, which may predispose DMD to instability. In summary, this study highlights the heterogeneous characteristics of the flanking sequences around the breakpoints and helps us to understand the mechanism underlying DMD gene instability.
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Distrofina/genética , Éxons , Rearranjo Gênico , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Adolescente , Alelos , Substituição de Aminoácidos , Povo Asiático/genética , Criança , Pré-Escolar , China , Pontos de Quebra do Cromossomo , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Instabilidade Genômica , Genótipo , Humanos , Masculino , Distrofia Muscular de Duchenne/epidemiologia , FenótipoRESUMO
Farber disease (FD) is a rare lysosomal storage disorder caused by mutation of the ASAH1 gene. Classic symptoms of FD include subcutaneous nodules, joint pain and hoarseness. Most patients die during childhood. Here we report a 25-year-old female FD patient with rare osteolytic changes of bilateral hands and toes. Genetic analysis revealed novel compound heterozygous mutations in the ASAH1 gene (c.427T>G and c.358G>C). Further research is needed to elucidate the pathophysiological course.
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Ceramidase Ácida/genética , Lipogranulomatose de Farber/genética , Predisposição Genética para Doença , Doenças por Armazenamento dos Lisossomos/genética , Adulto , Criança , China , Feminino , Humanos , Doenças por Armazenamento dos Lisossomos/patologia , MutaçãoRESUMO
The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.
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Consenso , Testes Genéticos/métodos , Testes Genéticos/normas , Guias de Prática Clínica como Assunto , China , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype-phenotype correlation in GSD III.
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Sistema da Enzima Desramificadora do Glicogênio/genética , Doença de Depósito de Glicogênio Tipo III/diagnóstico , Doença de Depósito de Glicogênio Tipo III/genética , Mutação , Adolescente , Alelos , Sequência de Aminoácidos , Povo Asiático/genética , Criança , Pré-Escolar , China , Biologia Computacional/métodos , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Fenótipo , Sítios de Splice de RNA , Adulto JovemRESUMO
BACKGROUND: Kabuki syndrome is a rare hereditary disease affecting multiple organs. The causative genes identified to date are KMT2D and KDMA6. The aim of this study is to evaluate the clinical manifestations and the spectrum of mutations of KMT2D. METHODS: We retrospectively retrieved a series of eight patients from two hospitals in China and conducted Sanger sequencing for all of the patients and their parents if available. We also reviewed the literature and plotted the mutation spectrum of KMT2D. RESULTS: The patients generally presented with typical clinical manifestations as previously reported in other countries. Uncommon symptoms included spinal bifida and Dandy-Walker malformation. With respect to the mutations, five mutations were found in five patients, including two frameshift indels, one nonsense mutation and two missense mutations. CONCLUSIONS: This is the first case series on Kabuki syndrome in Mainland China. Unusual symptoms, such as spinal bifida and Dandy-Walker syndrome, suggested that neurological developmental defects may accompany Kabuki syndrome. This case series helps broaden the mutation spectrum of Kabuki syndrome and adds information regarding the manifestations of Kabuki syndrome.
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Anormalidades Múltiplas/genética , Povo Asiático/genética , Face/anormalidades , Doenças Hematológicas/genética , Mutação , Doenças Vestibulares/genética , Anormalidades Múltiplas/patologia , Anormalidades Múltiplas/fisiopatologia , Criança , Pré-Escolar , Proteínas de Ligação a DNA/genética , Face/patologia , Face/fisiopatologia , Feminino , Doenças Hematológicas/patologia , Doenças Hematológicas/fisiopatologia , Humanos , Lactente , Masculino , Proteínas de Neoplasias/genética , Doenças Vestibulares/patologia , Doenças Vestibulares/fisiopatologiaAssuntos
Arteriopatias Oclusivas/epidemiologia , Doenças Arteriais Cerebrais/epidemiologia , Doença de Depósito de Glicogênio Tipo I/epidemiologia , Adolescente , Arteriopatias Oclusivas/diagnóstico por imagem , Doenças Arteriais Cerebrais/diagnóstico por imagem , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Tontura , Feminino , Doença de Depósito de Glicogênio Tipo I/diagnóstico por imagem , Cefaleia , Humanos , Deficiência Intelectual , Ataque Isquêmico Transitório , Angiografia por Ressonância Magnética , Masculino , Prevalência , Acidente Vascular CerebralRESUMO
Fanconi-Bickel syndrome (FBS, OMIM 227810), a rare autosomal recessive disorder of carbohydrate metabolism, is caused by SLC2A2 (GLUT2) mutations. The study reported 3 cases of FBS who were confirmly diagnosed by SLC2A2 gene analysis. The three patients showed typical features like glycogen storage disease and proximal renal tubular nephropathy. Homozygous splice-site mutation IVS8+5G>C (c.1068+5 G>C) was found in patient A and homozygous nonsense mutation c.1194T>A (p.Tyr398X) in patient B. Patient C harboured a missense mutation c.380C>A (p.Ala127Asp) and a de novo insertion c.970dupT (p.324TyrfsX392) which was not inherited from her parents. Four mutations were identified in the 3 Chinese FBS patients. Except IVS8+5G>C mutation, the other 3 mutations were novel in Chinese population. To the best of our knowledge, patient C may be the first FBS case worldwide with de novo mutation.
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Síndrome de Fanconi/genética , Transportador de Glucose Tipo 2/genética , Feminino , Humanos , MutaçãoRESUMO
OBJECTIVE: Hereditary multiple exostoses (HME) is an autosomal dominant monogenic disorder of paraplasia ossium. Mutations in EXT1 and EXT2 have been suggested to be responsible for over 70% of HME cases. This study aimed to analyze the clinical features and pathogenic mutations in a Chinese family with HME (6 patients in 24 members of 3 generations) and to review the relative literature regarding mutations in EXT1 and EXT2 in the Chinese population. METHODS: Clinical pedigree dada from a Chinese family of HME were collected and analysed. EXT gene mutations in this pedigree assessed by PCR and sequencing. Pubmed and Wanfang (a Chinese database) were searched for the literature related to gene mutations in Chinese HME patients. RESULTS: In the pedigree analyzed, the age of onset of HME was becoming younger, the disease was becoming more severe, and the number of osteochondromas was increasing, in successive generations. A splicing mutation IVS5+1G>A, first identified in Chinese population, was found in all diseased members of this pedigree. According the currently available literature, EXT1 and EXT2 mutations have been detected in 29% (26/90) and 43% (39/90) Chinese families with HME. CONCLUSIONS: HME starts earlier and becomes more severe and extensive with each successive generation in members of the pedigree analyzed. A splicing mutation, IVS5+1G>A, of EXT1, first identified in Chinese population, may be responsible for HME in the studied pedigree. EXT1 and EXT2 mutation rates may be different between the Chinese and Western populations.
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Exostose Múltipla Hereditária/genética , Mutação , N-Acetilglucosaminiltransferases/genética , Adolescente , Adulto , Idoso , Processamento Alternativo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
The clinical data of three Chinese children who had been definitely diagnosed with X-link dominate hypophosphatemic rickets (XLH) by gene mutation analysis of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) were retrospectively studied and the relevant literature was reviewed. PHEX gene mutations were detected in all 3 XLH children; a nonsense mutation (c.58C>T) in one case and splicing mutations (c.1645+1G>A, c.436+1G>A) in the other two cases. Among these mutations, c.436+1G>A was novel. As of January 2014, a total of 329 PHEX gene mutations were reported, primarily within three mutation hot spots, throughout the world. Missense mutations accounted for the highest proportion (24%) among all mutations. There is literature showing geographic differences in the total number of XLH subjects and PHEX mutation types across the world. In the current literature, 89 cases of XLH with 28 types of PHEX mutations have been reported in the population of mainland China. Exon 22 is the most frequent mutation site (18%) and missense mutations are the most common type of mutations (61%). It is concluded that exon 22 is the mutation hot spot and missense mutation is the most common type of mutation in the PHEX gene in Chinese XLH patients and that c.436+1G>A detected in this study is a novel PHEX gene mutation in Chinese with XLH.
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Raquitismo Hipofosfatêmico Familiar/genética , Mutação , Endopeptidase Neutra Reguladora de Fosfato PHEX/genética , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
OBJECTIVES: We aimed to determine the prevalence of cardiovascular involvement in our Blau syndrome (BS) cohort and provide detailed analysis of their cardiovascular manifestations and outcome. We also tried to find out the risk factors for developing cardiovascular involvement. METHODS: Clinical manifestations, laboratory findings, and treatments were reviewed. Clinical features were compared between children with cardiovascular involvement and those without angiocardiopathy. RESULTS: A total of 38 BS children were eligible for final analysis. Among them, 13 (34.2%) developed Takayasu-like vasculitis and/or cardiopathy. Compared with those without angiocardiopathy, recurrent fever was more frequent in BS patients with cardiovascular involvement (p < 0.001). What is more, tumor necrosis factor alpha antagonists (anti-TNF) were more urgently needed in children with cardiovascular involvement (p = 0.015). BS patients with cardiovascular involvement include 4 with Takayasu-like vasculitis and 9 with cardiopathy. The onset of cardiovascular manifestations ranged from 0.75 to 18.5 years of age, with most cases occurring before school period. Symptoms were elusive and lacked specificity, such as dizziness, short of breath, and edema. Some patients were even identified because of the unexpected hypertension during follow-up. Cardiopathy and vasculitis occurred in patients with different genotypes. Imaging changes were discovered before the presentation of the typical triad in 3/4 patients with Takayasu-like vasculitis. Three children developed left ventricular dysfunction with decreased left ventricular ejection fraction. Combination of glucocorticoids and methotrexate with anti-TNF agents is a common treatment option for these BS patients. In the cohort, BS-related cardiovascular involvement was controlled well, with cardiac structural and functional abnormalities completely recovered and slower progression of vasculitis lesions. CONCLUSION: Cardiovascular manifestations is not rare in BS patients. Because of its insidious onset, a systematic and comprehensive assessment of cardiovascular involvement should be performed in newly diagnosed patients with BS. Aggressive initiation of anti-TNF agents may be beneficial to improve the prognosis. Key Points ⢠About 34.2% patients with Blau syndrome developed Takayasu-like vasculitis and/or cardiopathy. ⢠Compared with those without angiocardiopathy, recurrent fever and application of anti-TNF agents were more frequent in BS patients with cardiovascular involvement (p < 0.001, p = 0.015) ⢠Regular assessment of cardiovascular involvement is extremely necessary because of its insidious onset.
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Artrite , Cardiopatias , Sarcoidose , Sinovite , Arterite de Takayasu , Uveíte , Vasculite , Criança , Humanos , Inibidores do Fator de Necrose Tumoral , Volume Sistólico , Função Ventricular Esquerda , Fenótipo , Arterite de Takayasu/complicações , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/diagnósticoRESUMO
Klebsiella pneumoniae (K. pneumoniae) is recognized as a zoonotic pathogen with an increasing threat to livestock and poultry. However, research on K. pneumoniae of animal origin remains limited. To address the gap, a comprehensive investigation was carried out by collecting a total of 311 samples from the farms of four animal species (dairy cow, chicken, sheep, and pig) in selected areas of Xinjiang, China. Isolates were identified by khe gene amplification and 16S rRNA gene sequencing. Genotyping of K. pneumonia isolates was performed using wzi typing and multilocus sequence typing (MLST). PCR was employed to identify virulence and resistance genes. An antibiotic susceptibility test was conducted using the Kirby-Bauer method. The findings revealed an isolation of 62 K. pneumoniae strains, with an average isolation rate of 19.94%, with the highest proportion originating from cattle sources (33.33%). Over 85.00% of these isolates harbored six virulence genes (wabG, uge, fimH, markD, entB, and ureA); while more than 75.00% of isolates possessed four resistance genes (blaTEM, blaSHV, oqxA, and gyrA). All isolates exhibited complete resistance to ampicillin and demonstrated substantial resistance to sulfisoxazole, amoxicillin/clavulanic acid, and enrofloxacin, with an antibiotic resistance rate of more than 50%. Furthermore, 48.39% (30/62) of isolates were classified as multidrug-resistant (MDR) strains, with a significantly higher isolation rate observed in the swine farms (66.67%) compared to other farms. Genetic characterization revealed the classification of the 62 isolates into 30 distinct wzi allele types or 35 different sequence types (STs). Notably, we identified K. pneumoniae strains of dairy and swine origin belonging to the same ST42 and wzi33-KL64 types, as well as strains of dairy and chicken origin belonging to the same wzi31-KL31-K31 type. These findings emphasize the widespread occurrence of drug-resistant K. pneumoniae across diverse animal sources in Xinjiang, underscoring the high prevalence of multidrug resistance. Additionally, our results suggest the potential for animal-to-animal transmission of K. pneumoniae and there was a correlation between virulence genes and antibiotic resistance genes. Moreover, the current study provides valuable data on the prevalence, antibiotic resistance, and genetic diversity of K. pneumoniae originating from diverse animal sources in Xinjiang, China.
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Wilson disease (WD) is an autosomal recessive inherited disease caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in 114 individuals of Chinese Han population living in north China who were diagnosed as WD. Totally, we identified 36 mutations and 11 single-nucleotide polymorphisms (SNPs), of which 14 mutations have never been reported previously and 5 were firstly described in Chinese. Among these, p.R778L (21.5%), p.A874V (7.5%) and p.P992L (6.1%) were the most frequent mutations. A genotype of p.L770L+p.R778L+p.P992L was the most frequent triple mutations and two pairs of mutations, p.L770L/p.R778L and p.A874V/p.I929V, were closely related. In addition, a database was established to summarize all ATP7B mutations, including those reported previously and those identified in this study. Popular algorithms were used to predict the functional effects of these mutations, and finally, by comparative genomics approaches, we predicted a group of mutation hot spots for ATP7B. Our study will broaden our knowledge about ATP7B mutations in WD patients in north China, and be helpful for clinical genetic testing.
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Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Degeneração Hepatolenticular/genética , Mutação , Adolescente , Adulto , Algoritmos , Criança , China , ATPases Transportadoras de Cobre , Etnicidade/genética , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Background: Mucopolysaccharidosis Type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This report conducted a retrospective analysis to investigate the clinical characteristics, genotypes and management strategies in a large cohort of Chinese patients with MPS II. Methods: In this study, we explored 130 Chinese patients with MPS II between September 2008 and April 2022. Clinical manifestations, auxiliary examination, IDS pathogenic gene variants and IDS enzyme activity, surgical history were analysed in the study. Results: A total of 130 patients were enrolled and the mean age at diagnosis was 5 years old. This study found the most common symptoms in our patients were claw-like hands, followed by coarse facial features, birthmarks (Mongolian spot), delayed development, inguinal or umbilical hernia. The most commonly cardiac manifestations were valve abnormalities, which were mitral/tricuspid valve regurgitation (71.9%) and aortic/pulmonary valve regurgitation (36.8%). We had found 43 different IDS pathogenic gene variants in 55 patients, included 16 novel variants. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55). A total of 50 patients (38.5%) underwent surgical treatment, receiving a total of 63 surgeries. The average age of first surgery was 2.6 years, and the majority of surgery (85.7%, 54/63) was operated before 4 years old. The most common and earliest surgery was hernia repair. Three patients were died of respiratory failure. Conclusion: This study provided additional information on the clinical, cardiac ultrasound and surgical procedure in MPS II patients. Our study expanded the genotype spectrum of MPS II. Based on these data, characterization of MPS II patients group could be used to early diagnosis and treatment of the disease.
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Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1)-related multiple arterial stenoses is a rare clinical syndrome in which global arterial calcification begins in infancy, with a high probability of early mortality, and hypophosphatemic rickets develops later in childhood. The vascular status of an ENPP1-mutated patient when they enter the rickets phase has not been thoroughly explored. In this study, we presented a case of an adolescent with an ENPP1 mutation who complained of uncontrolled hypertension. Systematic radiography showed renal, carotid, cranial, and aortic stenoses as well as random calcification foci on arterial walls. The patient was incorrectly diagnosed with Takayasu's arteritis, and cortisol therapy had little effect on reducing the vascular stenosis. As a result, phosphate replacement, calcitriol substitution, and antihypertensive medication were prescribed, and the patient was discharged for further examination. This research presented the vascular alterations of an ENPP1-mutanted patient, and while there is less calcification, intimal thickening may be the primary cause of arterial stenosis.
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BACKGROUND: Progressive pseudorheumatoid dysplasia (PPRD) is a rare genetic disease with autosomal recessive inheritance. There was a lack of genotype-phenotype correlation data from the Chinese population. This study aimed to identify the genotype and phenotype characteristics of Chinese PPRD patients and to conduct a genotype-phenotype analysis of Chinese PPRD patients. METHODS: Genetic analysis was performed for suspected PPRD patients from Peking Union Medical College Hospital. Medical records were collected from the electronic medical record system and patient-held portable health records. Published Chinese PPRD cases were gathered from both international and Chinese local databases. We collected demographic information, genetic variants, clinical manifestations, and imaging characteristics for further analysis. RESULTS: We included 105 Chinese PPRD patients in the current study. Thirty-three variants, including nine novels and five hotspot variants, were identified, with 26/33 (79%) variants exclusively seen in the Chinese population. Chinese PPRD patients share a phenotype similar to that in international reports. Joint involvement may progress with age (R2 = 0.2541). Long bone shortening and severe deformities occur in three patients with biallelic null variants, of which at least one variant is located in exon 2. Among hotspot variants, c.624dupA (p.C209Mfs*21) were associated with later onset and more involved joints. Elbow joints were more likely to be affected in patients carrying c.624dupA (p.C209Mfs*21) and c.866dupA (p.S209Efs*13). Shoulder joints are more likely to be involved in patients with biallelic null variants (P = 0.027). CONCLUSIONS: Chinese PPRD patients share a unique mutation spectrum. Among the five hotspot variants, c.624dupA is associated with later onset of disease, more extensive joint involvement, and a tendency to affect elbow joints. Biallelic null variants with at least one variant in exon 2 could be a likely cause of long bone shortening and severe deformities.
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População do Leste Asiático , Artropatias , Humanos , População do Leste Asiático/genética , Genótipo , Mutação , Fenótipo , Estudos Retrospectivos , Artropatias/congênito , Artropatias/genéticaRESUMO
BACKGROUND: Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader-Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. METHODS: A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. RESULTS: Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. CONCLUSION: Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.
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Hormônio do Crescimento Humano , Síndrome de Prader-Willi , Criança , Pré-Escolar , Humanos , Lactente , Antropometria , Índice de Massa Corporal , Peso Corporal , Hormônio do Crescimento Humano/uso terapêutico , Hormônio do Crescimento Humano/efeitos adversos , Síndrome de Prader-Willi/tratamento farmacológico , Proteínas Recombinantes/efeitos adversosRESUMO
BACKGROUND: This study aimed to explore the clinical features of gout in adult patients with glycogen storage disease type Ia (GSD Ia). METHODS: Ninety-five adult patients with GSD Ia admitted to Peking Union Medical College Hospital were retrospectively analysed. A clinical diagnosis of GSD Ia was confirmed in all patients through gene sequencing. All patients had hyperuricaemia; 31 patients complicated with gout were enrolled, and 64 adult GSD Ia patients with asymptomatic hyperuricaemia were selected as a control group during the same period. Clinical characteristics were analysed and compared between the two groups. RESULTS: Thirty-one of the 95 patients had complications of gout (median age, 25 years; 11 (35.5%) females). All 31 patients had hepatomegaly, abnormal liver function, fasting hypoglycaemia, hyperuricaemia, hyperlipaemia, and hyperlacticaemia. A protuberant abdomen, growth retardation, recurrent epistaxis, and diarrhoea were the most common clinical manifestations. Among these 31 patients, 10 patients (32.3%) had gout as the presenting manifestation and were diagnosed with GSD Ia at a median time of 5 years (range, 1-14) after the first gout flare. The median age of gout onset was 18 years (range, 10-29). Fifteen of the 31 GSD Ia-related gout patients were complicated with gouty tophi, which has an average incidence time of 2 years after the first gouty flare. The mean value of the maximum serum uric acid (SUA) was 800.5 µmol/L (range, 468-1068). The incidence of gout in adult GSD Ia patients was significantly associated with the initial age of regular treatment with raw corn starch, the proportion of urate-lowering therapy initiated during the asymptomatic hyperuricaemic stage, maximum SUA level, and mean cholesterol level. CONCLUSIONS: Determination of GSD Ia should be performed for young-onset gout patients with an early occurrence of gouty tophi, especially in patients with hepatomegaly, recurrent hypoglycaemia, or growth retardation. Early detection and long-term regulatory management of hyperuricaemia, in addition to early raw corn starch and lifestyle intervention, should be emphasized for GSD Ia patients in order to maintain good metabolic control. TRIAL REGISTRATION: Retrospectively registered.