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We retrospectively analyzed National Health Insurance claims data (January 2002-December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.
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Asma , Displasia Broncopulmonar , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Masculino , Feminino , Recém-Nascido Prematuro , Prevalência , Estudos Retrospectivos , Asma/tratamento farmacológico , Asma/epidemiologia , Asma/etiologia , Fatores de Risco , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Prescrições de Medicamentos , Displasia Broncopulmonar/epidemiologia , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Central precocious puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis but its major cause remains unclear. Studies have indicated an association between chronic environmental exposure to endocrine-disrupting chemicals and pubertal onset. Essential oil is widely used in homes worldwide for relief of respiratory symptoms, stress, and/or sleep disturbance. METHODS: To evaluate this association, we compared the hormone levels and timing of vaginal opening (VO) in female rats exposed to lavender oil (LO) through different routes (study groups: control, LO nasal spray [LS], and indoor exposure to LO [LE]) during the prepubertal period. The body weights of the animals were also compared every 3 days until the day of VO, at which time gonadotropin levels and internal organ weights were assessed. RESULTS: The LS group showed early VO at 33.8 ± 1.8 days compared with the control (38.4 ± 2.9 days) and LE (36.6 ± 1.5 days) groups. Additionally, luteinizing hormone levels were significantly higher in the LE and LS groups than those in the control group. Body weights did not differ significantly among the groups. CONCLUSION: Inhalation exposure to an exogenic simulant during the prepubertal period might trigger early pubertal onset in female rats. Further evaluation of exposure to other endocrine-disrupting chemicals capable of inducing CPP through the skin, orally, and/or nasally is warranted.
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Lavandula/efeitos adversos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/efeitos adversos , Óleos de Plantas/administração & dosagem , Óleos de Plantas/efeitos adversos , Puberdade Precoce/induzido quimicamente , Administração por Inalação , Animais , Feminino , Distribuição Aleatória , RatosRESUMO
BACKGROUND: The switch/sucrose nonfermenting (SWI/SNF) complex is an adenosine triphosphate-dependent chromatin-remodeling complex associated with the regulation of DNA accessibility. Germline mutations in the components of the SWI/SNF complex are related to human developmental disorders, including the Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and nonsyndromic intellectual disability. These disorders are collectively referred to as SWI/SNF complex-related intellectual disability disorders (SSRIDDs). METHODS: Whole-exome sequencing was performed in 564 Korean patients with neurodevelopmental disorders. Twelve patients with SSRIDDs (2.1%) were identified and their medical records were retrospectively analyzed. RESULTS: ARID1B, found in eight patients, was the most frequently altered gene. Four patients harbored pathogenic variants in SMARCA4, SMARCB1, ARID2, and SMARCA2. Ten patients were diagnosed with CSS, and one patient without a typical phenotype was diagnosed with ARID1B-related nonsyndromic intellectual disability. Another patient harboring the SMARCA2 pathogenic variant was diagnosed with NCBRS. All pathogenic variants in ARID1B were truncating, whereas variants in SMARCA2, SMARCB1, and SMARCA4 were nontruncating (missense). Frequently observed phenotypes were thick eyebrows (10/12), hypertrichosis (8/12), coarse face (8/12), thick lips (8/12), and long eyelashes (8/12). Developmental delay was observed in all patients, and profound speech delay was also characteristic. Agenesis or hypoplasia of the corpus callosum was observed in half of the patients (6/12). CONCLUSIONS: SSRIDDs have a broad disease spectrum, including NCBRS, CSS, and ARID1B-related nonsyndromic intellectual disability. Thus, SSRIDDs should be considered as a small but important cause of human developmental disorders.
Assuntos
Anormalidades Múltiplas/genética , Face/anormalidades , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Hipotricose/genética , Deficiência Intelectual/genética , Micrognatismo/genética , Pescoço/anormalidades , Fenótipo , Fácies , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , República da CoreiaRESUMO
BACKGROUND: Glycogen storage disease (GSD) Ia, caused by mutations in the glucose-6-phosphatase (G6PC) gene, is characterized by hepatomegaly, hypoglycemia, lactic acidosis, dyslipidemia, and hyperuricemia. This study aimed to investigate clinical and molecular features and late complications in Korean patients with GSD Ia. RESULTS: Fifty-four Korean patients (33 males and 21 females) from 47 unrelated families, who were diagnosed with GSD Ia, based on genetic and biochemical data, between 1999 and 2017, were included in this study. The median age at diagnosis was 3.9 years (range: 5 months to 42 years), and the follow-up period was 8.0 ± 6.8 years. Most patients presented with hepatomegaly during infancy, but hypoglycemic symptoms were not predominant. Genetic analysis showed that all the patients had at least one c.648G > T allele. Homozygous c.648G > T mutations in the G6PC gene were identified in 34 families (72.3%), and compound heterozygotes with c.648G > T were found in the other families. The allele frequency of c.648G > T was 86.2% (81/94), and p.F51S, p.R83H, p.G122D, p.Y128*, p.G222R, and p.T255A were identified. Of 26 adult patients, 14 had multiple hepatic adenomas, and two were diagnosed with hepatocellular carcinoma. Thirteen patients showed renal complications, and seven patients presented gout, despite preventive allopurinol treatment. Twelve patients had osteoporosis, and two patients had pulmonary hypertension. The final heights were 157.9 cm (standard deviation score: - 3.1) in males and 157.8 cm (standard deviation score: - 0.6) in females. CONCLUSION: In our Korean patients with GSD Ia, the most common mutation in the G6PC gene was c.648G > T, suggesting a founder effect. Because of only mild hypoglycemia, the patients tended to be diagnosed late. Thus, adult patients with GSD Ia eventually developed diverse and serious complications, which indicates a need for careful monitoring and proper management of this disease.
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Glucose-6-Fosfatase , Doença de Depósito de Glicogênio Tipo I , Adulto , Feminino , Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/genética , Humanos , Masculino , Mutação/genética , República da CoreiaRESUMO
May-Hegglin anomaly (MHA) is a rare autosomal dominant disorder caused by a mutation in the myosin heavy chain 9 (MYH9) gene. MHA patients have variable clinical manifestations including thrombocytopenia, renal injury, hearing impairment, and cataracts. We describe a 25-year-old man with isolated thrombocytopenia initially. He experienced recurrent seizures with stable thrombocytopenia after the first seizures related to intracranial hemorrhage. He was identified a novel c.3452C>T mutation by targeted exome sequencing. If a patient with thrombocytopenia shows recurrent seizures as well as renal, hearing, visual symptoms, MHA should be suspected and the targeted exome sequencing is considered an effective diagnostic tool.
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Perda Auditiva Neurossensorial/genética , Cadeias Pesadas de Miosina/genética , Convulsões/genética , Trombocitopenia/congênito , Adulto , Perda Auditiva Neurossensorial/complicações , Humanos , Masculino , Mutação de Sentido Incorreto , Trombocitopenia/complicações , Trombocitopenia/genética , Sequenciamento do ExomaRESUMO
RATIONALE: Infantile-onset hypertrophic cardiomyopathy (HCMP) should be considered a largely genetic condition, although its onset is most often triggered by infection. Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive inborn error of mitochondrial fatty acid ß-oxidation that often causes severe cardiomyopathy and/or sudden death during the neonatal period. PATIENT CONCERNS: Herein, we report an infant with VLCAD deficiency who presented with severe cardiac manifestations, including massive pericardial effusion and HCMP. The subject's older sister died of unknown causes at three days of age; however, the subject exhibited a normal tandem mass-spectrometry profile during the neonatal period. DIAGNOSES: During her later cardiac presentation, the subject's C-14 and C-18 levels became elevated, and she was determined, via the conducted molecular analysis, to harbor a novel homozygous frameshift mutation (c.103_112dup) in ACADVL. INTERVENTIONS: After VLCAD deficiency diagnosis, the subject was treated with the administration of a medium chain triglyceride formula and fluid therapy. OUTCOMES: The subject's cardiac status was markedly improved by the dietary intervention and fluid therapy. LESSONS: This report highlights that genetic mutations should be investigated as possible causes of infantile-onset HCMP, and that early diagnosis and intervention can prevent mortality for patients with VLCAD deficiency.
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Acil-CoA Desidrogenase de Cadeia Longa/deficiência , Mutação da Fase de Leitura , Hipertrofia Ventricular Esquerda/etiologia , Erros Inatos do Metabolismo Lipídico/diagnóstico , Erros Inatos do Metabolismo Lipídico/genética , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Derrame Pericárdico/etiologia , Acil-CoA Desidrogenase de Cadeia Longa/genética , Síndrome Congênita de Insuficiência da Medula Óssea , Diagnóstico Tardio , Feminino , Hidratação , Humanos , Hipertrofia Ventricular Esquerda/terapia , Lactente , Erros Inatos do Metabolismo Lipídico/complicações , Erros Inatos do Metabolismo Lipídico/terapia , Doenças Mitocondriais/complicações , Doenças Mitocondriais/terapia , Doenças Musculares/complicações , Doenças Musculares/terapia , Derrame Pericárdico/terapia , Triglicerídeos/uso terapêuticoRESUMO
Prolactinoma is a benign tumor of the pituitary gland that rarely occurs in children and adolescents; thus, the clinical spectrum and long-term prognosis in these patients remain unknown. This study was performed to investigate the long-term outcomes of medical treatment and the prognostic factors for remission and relapse in children and adolescents with prolactinoma. Three male subjects and four female subjects between the ages of 7- and 17-years-old were included in this study. The mean initial serum prolactin level was 443 ± 251.8 ng/mL (range, 152-946 ng/mL). During the follow-up period (range, 0.6-20 years), a dopamine agonist was administered, and surgery or radiotherapy was performed in cases of resistance to medical treatment or relapse. Unlike female subjects with macroadenoma who often exhibit a good clinical course, two male subjects with early onset macroadenoma presented with visual disturbances. These subjects showed resistance to medical therapy and relapsed, eventually requiring surgical removal and radiotherapy; one of the subjects manifested a metastatic thrombus in the internal jugular vein. In conclusion, pediatric prolactinoma exhibits a broad clinical spectrum, a relatively high incidence of macroadenoma, resistance to medical therapy, and frequent tumor relapses. In addition, a poor prognosis appears to be correlated with male sex, age at disease onset, and histopathological characteristics.
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Agonistas de Dopamina/uso terapêutico , Neoplasias Hipofisárias/diagnóstico , Prolactina/sangue , Prolactinoma/diagnóstico , Adolescente , Idade de Início , Criança , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Fatores SexuaisRESUMO
Cushing disease in children and adolescents, especially with multiple pituitary adenomas (MPAs), is very rare. We report 17-year-old boy with MPAs. He presented with a vertebral compression fracture, weight gain, short stature, headache, and hypertension. On magnetic resonance imaging (MRI), only a left pituitary microadenoma was found. After surgery, transient clinical improvement was observed but headache and hypertension were observed again after 3 months later. Follow-up MRI showed a newly developed right pituitary microadenoma 6 months after the surgery. The need for careful clinical and radiographic follow-up should be emphasized in the search for potential MPAs in patients with persistent Cushing disease.
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Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males. Each diagnosis was based on an enzyme assay and GLA gene mutation analysis.The mean age at presentation was 24 years (range, 5-65 years); however, the diagnoses were delayed by 21â±â19 years after the onset of symptoms. Those patients with late-onset Fabry disease were diagnosed by family screening or milder symptoms at a later age. Forty different mutations were identified: 20 missense (50%), 10 nonsense (25%), 8 frameshift (20%), and 2 splice site (5%) mutations. Five of them were novel. IVS4+919G>A (c.936+919 G>A) was not detected among the 6505 alleles via newborn screening using dried blood spots. Enzyme replacement therapy (ERT) was performed in all the males and pediatric patients, whereas 75% of the symptomatic females underwent ERT for 4.2â±â3.6 years.This study described the demographic data, wide clinical spectrum of phenotypes, and GLA mutation spectrum of Fabry disease in Korea. Most of the patients had classical Fabry disease, with a 4 times higher incidence than that of late-onset Fabry disease, indicating an underdiagnosis of mild, late-onset Fabry disease.
Assuntos
Doença de Fabry/epidemiologia , Doença de Fabry/genética , Mutação , alfa-Galactosidase/genética , Adolescente , Idade de Início , Idoso , Criança , Pré-Escolar , Erros de Diagnóstico , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/tratamento farmacológico , Feminino , Estudos de Associação Genética , Humanos , Incidência , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Triagem Neonatal , Fenótipo , República da Coreia/epidemiologia , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Methionine adenosyltransferase (MAT) I/III deficiency can be inherited as autosomal dominant (AD) or as recessive (AR) traits in which mono- or biallelic MAT1A mutations have been identified, respectively. Although most patients have benign clinical outcomes, some with the AR form have neurological deficits. Here we describe 16 Korean patients with MAT I/III deficiency from 15 unrelated families identified by newborn screening. Ten probands had the AD MAT I/III deficiency, while six had AR MAT I/III deficiency. Plasma methionine (145.7 µmol/L versus 733.2 µmol/L, P < 0.05) and homocysteine levels (12.3 µmol/L versus 18.6 µmol/L, P < 0.05) were lower in the AD type than in AR type. In addition to the only reported AD MAT1A mutation, p.Arg264His, we identified two novel AD mutations, p.Arg249Gln and p.Gly280Arg. In the AR type, four previously reported and two novel mutations, p.Arg163Trp and p.Tyr335*, were identified. No exonic deletions were found by quantitative genomic polymerase chain reaction (PCR). Three-dimensional structural prediction programs indicated that the AD-type mutations were located on the dimer interface or in the substrate binding site, hindering MAT I/III dimerization or substrate binding, respectively, whereas the AR mutations were distant from the interface or substrate binding site. These results indicate that the AD or AR MAT I/III deficiency is correlated with clinical findings, substrate levels and structural features of the mutant proteins, which is important for the neurological management and genetic counseling of the patients.
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Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Gαgust(-/-) mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI-H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Células Enteroendócrinas/efeitos dos fármacos , Ginsenosídeos/farmacologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hiperglicemia/prevenção & controle , Animais , Linhagem Celular Tumoral , Células Enteroendócrinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/sangue , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/complicações , Immunoblotting , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interferência de RNA , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transducina/deficiência , Transducina/genéticaRESUMO
Menkes disease is a very rare X-linked copper metabolism disorder that results from an ATP7A gene mutation. With the advent of subcutaneous copper-histidine therapy, the early diagnosis of Menkes disease becomes of utmost importance for patients' prognosis. In the present study, the clinical characteristics of 12 Korean patients with Menkes disease (11 males and 1 female from 11 unrelated families) were described along with the mutation spectrum. Only 2 male patients were diagnosed in the neonatal period, and the other male patients were diagnosed at age 4.3 ± 1.9 months. The presenting signs included depigmented kinky hair, neurologic deficits, and hypotonia. Serum copper and ceruloplasmin levels were markedly decreased. Intracranial vessels were dilated with tortuosity and accompanied by regional cerebral infarctions, even at an early age. Of note, the female patient was diagnosed at age 18 months, during the evaluation for developmental delay, by characteristic MRA findings, biochemical profiles, and genetic evaluation. A total of 11 ATP7A mutations were identified, including five previously unreported mutations. Most mutations were truncated (except 1 missense mutation), including 3 frameshift, 2 nonsense, 3 large deletion, and 2 splice-site variants. The age at commencement of copper-histidine treatment was variable among patients age 7.3 ± 7.5 (0.5-27) months. Despite the treatment, seven patients died before age 5 years, and the remaining patients were severely retarded in neurodevelopment. The poor outcomes of our patients might be related to delayed therapy, but severe ATP7A mutations should be noted as well.
Assuntos
Adenosina Trifosfatases/genética , Proteínas de Transporte de Cátions/genética , Cobre/uso terapêutico , Histidina/uso terapêutico , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Infarto Cerebral/etiologia , Ceruloplasmina/análise , Cromossomos Humanos X/genética , Códon sem Sentido , Cobre/sangue , ATPases Transportadoras de Cobre , Análise Mutacional de DNA , Diagnóstico Precoce , Intervenção Médica Precoce , Éxons/genética , Feminino , Mutação da Fase de Leitura , Humanos , Lactente , Recém-Nascido , Injeções Subcutâneas , Coreia (Geográfico) , Angiografia por Ressonância Magnética , Masculino , Síndrome dos Cabelos Torcidos/genética , Mutação de Sentido Incorreto , Sítios de Splice de RNA/genética , Deleção de Sequência , Falha de Tratamento , Inativação do Cromossomo XRESUMO
KBG syndrome is a very rare genetic disorder characterized by macrodontia of upper central incisors, global developmental delay, distinctive craniofacial features, short stature, and skeletal anomalies. Ankyrin repeat domain 11 gene (ANKRD11) has recently been identified as a causal factor of this syndrome. We describe a 6-yr-old Korean boy with features of KBG syndrome. The patient had a short stature, macrodontia, dysmorphic facial features, speech and motor delay with intellectual disability, and partial seizures as indicated by the electroencephalogram, but he was neither autistic nor had autism spectrum disorders. Using high-resolution oligonucleotide array comparative genomic hybridization, we identified a heterozygous 240-kb deletion at 16q24.3 corresponding to ANKRD11. This patient provided additional evidence on the influence of ANKRD11 in KBG syndrome and suggested that deletion limited to ANKRD11 is unlikely to cause autism.
Assuntos
Anormalidades Múltiplas/genética , Povo Asiático/genética , Doenças do Desenvolvimento Ósseo/genética , Deficiência Intelectual/genética , Proteínas Repressoras/genética , Anormalidades Dentárias/genética , Anormalidades Múltiplas/diagnóstico , Doenças do Desenvolvimento Ósseo/diagnóstico , Criança , Cromossomos Humanos Par 16 , Hibridização Genômica Comparativa , Eletroencefalografia , Fácies , Deleção de Genes , Heterozigoto , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Fenótipo , República da Coreia , Anormalidades Dentárias/diagnósticoRESUMO
BACKGROUND: Artemisia capillaris (AC) has been recognized as one of the promising candidates for hepatoprotective, hypoglycemic, hypolipidemic, antiobesitic and anti-inflammatory therapeutic effectiveness. This study evaluated the inherent mechanism and anti-apoptotic activity of 30% ethanol extract of AC (AC extract) 100 µg/ml on free fatty acids (FFAs)-induced HepG2 cellular steatosis and lipoapoptosis. METHODS: Hepatic steatosis was induced by culturing HepG2 cells with a FFAs mixture (oleic and palmitic acid at the proportion of 2:1) for 24 h, thus ultimately giving rise to lipoapoptosis. Cell viability and lipid accumulation were detected by MTT assay and Oil Red O staining method respectively and Caspase-3, -9, Bax, Bcl-2, p-JNK and PUMA were measured for lipoapoptosis after 24 hours. RESULTS: AC extract significantly improved the FFAs-induced steatosis without cytotoxicity and Caspase-3, -9, Bax and Bcl-2 were modulated profitably to HepG2 cells after AC treatment. In addition, AC extract inhibited the activation of c-Jun NH2 terminal kinase (JNK) and PUMA, which mechanism is related to non-alcoholic steatohepatitis (NASH). CONCLUSIONS: Combined together, AC extract exerted an obvious hypolipidemic and anti-apoptotic effect, indicating that AC extract might have potential therapeutic herb against NASH.
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Apoptose/efeitos dos fármacos , Artemisia/química , Ácidos Graxos não Esterificados/administração & dosagem , Fígado Gorduroso/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos não Esterificados/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Células Hep G2 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Modelos Biológicos , Proteínas Proto-Oncogênicas/metabolismoRESUMO
PURPOSE: Lowe syndrome is a rare, X-linked recessive disorder caused by mutations in the OCRL gene. It involves multiple anatomic systems, particularly the eyes, central nervous system, and kidneys, and leads to profound growth failure and global developmental delay. This study evaluated the clinical and genetic characteristics of Korean patients with Lowe syndrome. METHODS: The clinical findings and results of genetic studies were reviewed for 12 male patients diagnosed with Lowe syndrome at a single medical institution. RESULTS: The mean age of the patients at presentation was 2.2 months (range, 0-4 months), although the diagnosis was delayed by a mean of 2.8 years (range, 0-9.7 years). The mean follow-up period was 9.0 years (range, 0.6-16.7 years). Nine mutations in OCRL were identified in 11 patients (92%), with three novel mutations. The main presentation was congenital cataract in both eyes necessitating early cataract removal in the 11 patients with impaired visual acuity. Profound short stature and developmental delay were observed in all patients, and seizures occurred in 50% of the patients. All patients suffered from proximal renal tubular dysfunction, and one patient developed chronic renal failure. Other manifestations included pathologic fracture (50%), cutaneous cysts (42%), and cryptorchidism (42%). However, there was no bleeding tendency, and none of the patients died during the study period. CONCLUSION: This study describes the clinical and genetic characteristics of Korean patients with Lowe syndrome. The observations are helpful for understanding the natural courses of Lowe syndrome and for appropriate genetic counseling.
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Non-immune hydrops fetalis is the most severe presenting feature of lysosomal storage disorders. However, it is difficult to identify the underlying condition because the different lysosomal storage diseases share many clinical features. A neonate with hydrops fetalis is described here. A lysosomal storage disorder was first suspected when the placental biopsy showed the presence of macrophages containing numerous cytoplasmic vacuoles. Subsequent comprehensive diagnostic processes and biochemical and molecular genetics characterization revealed a rare genetic cause, namely sialidosis type 2. Liquid chromatography-mass spectrometry revealed increased amounts of bound sialic acid in the urine. Pathogenic NEU1 mutations were detected. This is the first case with sialidosis type 2 ever known in the Korean population, exhibiting its most severe manifestation.
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Hidropisia Fetal/genética , Hidropisia Fetal/patologia , Doenças por Armazenamento dos Lisossomos/diagnóstico , Mucolipidoses/genética , Mutação/genética , Predisposição Genética para Doença , Humanos , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/etiologia , Recém-Nascido , Doenças por Armazenamento dos Lisossomos/etiologia , Doenças por Armazenamento dos Lisossomos/genética , Doenças por Armazenamento dos Lisossomos/patologia , Mucolipidoses/complicações , República da CoreiaRESUMO
Turner syndrome has multiple comorbidities such as osteoporosis, obesity, diabetes, hypothyroidism, and hypertension. As they are treatable conditions in Turner syndrome, early recognition and proper treatment should be needed. We report on a 23-year-old woman with Turner syndrome who presented with severe osteoporosis and hypercalcemia. Laboratory tests showed elevated levels of serum calcium and parathyroid hormone. Dual-energy X-ray absorptiometry showed severe osteopo-rosis (z score, -3.5). Ultrasound and (99m)Tc scintigraphy of parathyroid glands showed an adenoma in the right inferior gland. She was diagnosed with primary hyperparathyroidism due to an adenoma of the parathyroid gland. After excision of the adenoma, the patient's serum calcium and parathyroid hormone levels returned to normal. Although only a few cases of Turners syndrome with primary hyperparathyroidism have been reported, hyperparathyroidism should be considered in cases of Turner syndrome with severe osteoporosis and hypercalcemia.