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The incorporation of dynamic covalent bonds has been an attractive strategy to synthesize adaptive solid polymer electrolytes (SPEs). Here, we present molecular dynamics results concerning the relationship between ion transport and segmental dynamics for dynamic covalent cross-linked PEO-Li+ SPEs. To dissolve LiPF6 into PEO, a 1/r4-form approximation of ion-dipole interactions is employed as the solvation potential. Its parameters are estimated with the assistance of the Bayesian optimization algorithm and validated by comparing the resulting behaviors of PEO/LiPF6 with experimental observations. The dynamic associations of EO with Li+ and PF6- significantly reduce the segmental mobility of PEO, verifying the coupling of PEO segmental dynamics with ion transport. In order to reproduce the unique behaviors of associative covalent adaptive networks (CANs), the bond-exchange reaction is controlled by the collision probability and the user-defined activation energy (Ea ≥ 0) based on a hybrid of molecular dynamics and Monte Carlo methods. The dynamics of network topology, facilitated by the reshuffling of dynamic covalent bonds, is analyzed using graph theory. The network mesh size varies with time, which can be considered as one of the characteristics for associative CANs. The reshuffling of dynamic bonds releases the constraint from cross-linked structures, and enhances the long-range segmental mobility as well as the mobilities of Li+ and PF6-. By drawing comparisons with its conventionally cross-linked counterpart, the effect of dynamic-bond reshuffling on ion transport is studied for the dynamic covalent cross-linked PEO16-LiPF6 electrolyte in terms of self-diffusivities, cation transference number, and ionic conductivity.
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In this work, an environment-friendly core-shell material based on CDs@SiO2as the core and mesoporous ion-imprinted layer as the shell was reported. As a highly sensitive and accurate fluorescent sensor for the detection of Pb2+in environmental water, the composition combined ion imprinting technology with quantum dots to selectively quench the fluorescence of CDs by metal coordination in the presence of Pb2+, and the visual change of gradually weakening blue color could be observed by the naked eye for visual detection. The mesoporous structure significantly improved the detection recognition rate of CDs@SiO2@MIIPs.The molecularly imprinted sensor presented a favorable linear relationship over a Pb2+concentration range from 10 nmol l-1to 100 nmol l-1and a detection limit of 2.16 nmol l-1for Pb2+. The imprinting factor of the CDs@SiO2@MIIPs was 5.13. The sensor has a fast detection rate, is highly selective in the identification of Pb2+, and can be reused up to 10 times. The applicability of the method was evaluated by the determination of Pb2+in spiked environmental water samples with satisfactory results.
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Vitrimers are covalent adaptable networks, having many interesting versatile abilities with unprecedented potentials. Here, the combination of a low-Tg polymer system with dioxaborolane metathesis is used to develop catalyst-free vitrimers that can be stretched to more than 8900× their original length at a moderate stretching rate (≈50 mm min-1 ). Superstretchable vitrimers are prepared from biodegradable xylitol-based polyol oligomers and cross-linked by dioxaborolane linkages. They are also found to be remarkable in terms of mechanical strength and other properties, such as malleability, self-healing ability, puncture resistance, and processing stability. Furthermore, the repeated rearrangements of dioxaborolane linkages and hydrogen bonds give rise to efficient energy dissipation with a maximum efficiency of 88%, allowing the superstretchable vitrimers to be promising for energy absorbing applications.
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Enlace de Hidrógeno , CatálisisRESUMEN
Despite the large variety of modified nucleosides that have been reported, the preparation of constrained 4'-spirocyclic adenosine analogues has received very little attention. We discovered that the [2+2]-cycloaddition of dichloroketene on readily available 4'-exo-methylene furanose sugars efficiently results in the diastereoselective formation of novel 4'-spirocyclobutanones. The reaction mechanism was investigated via density functional theory (DFT) and found to proceed either via a non-synchronous or stepwise reaction sequence, controlled by the stereochemistry at the 3'-position of the sugar substrate. The obtained dichlorocyclobutanones were converted into nucleoside analogues, providing access to a novel class of chiral 4'-spirocyclobutyl adenosine mimetics in eight steps from commercially available sugars. Assessment of the biological activity of designed 4'-spirocyclic adenosine analogues identified potent inhibitors for protein methyltransferase target PRMT5.
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Adenosina/química , Nucleósidos/análogos & derivados , Nucleósidos/síntesis química , Carbohidratos/química , Reacción de Cicloadición , Teoría Funcional de la Densidad , Dicloroetilenos/química , Glicosilación , Metales/química , Estructura Molecular , Oxidación-Reducción , Estereoisomerismo , TermodinámicaRESUMEN
This study reports a boy with psychomotor retardation and epilepsy due to maternal phenylketonuria (PKU). The boy was admitted at the age of 20 months because of psychomotor retardation and epilepsy. He had seizures from the age of 1 year. His development quotient was 43. He presented with microcephaly, normal skin and hair color. Brain MRI scan showed mild cerebral white matter demyelination, broadening bilateral lateral ventricle and foramen magnum stricture. Chromosome karyotype, urine organic acids, blood amino acids and acylcarnitines were normal. His mother had mental retardation from her childhood. She presented with learning difficulties and yellow hair. Her premarriage health examinations were normal. She married a healthy man at age of 26 years. When she visited us at 28 years old, PKU was found by markedly elevated blood phenylalanine (916.54â µmol/L vs normal range 20-120â µmol/L). On her phenylalanine hydroxylase (PAH) gene, a homozygous mutations c.611A>G (p.Y204C) was identified, which confirmed the diagnosis of PAH-deficient PKU. Her child carries a heterozygous mutation c.611A>G with normal blood phenylalanine. Her husband had no any mutation on PAH. It is concluded that family investigation is very important for the etiological diagnosis of the children with mental retardation and epilepsy. Carefully clinical and metabolic survey should be performed for the parents with mental problems to identify parental diseases-associated child brain damage, such as maternal PKU.
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Epilepsia/etiología , Discapacidad Intelectual/etiología , Fenilcetonuria Materna , Adulto , Femenino , Humanos , Lactante , Masculino , Fenilalanina Hidroxilasa/genética , EmbarazoRESUMEN
This article describes the formation of dopamine-melanin thin films (50-200 nm thick) at an air/dopamine solution interface under static conditions. Beneath these films, spherical melanin granules formed in bulk liquid phase. The thickness of dopamine-melanin films at the interface relied mainly on the concentration of dopamine solution and the reaction time. A plausible mechanism underlining dopamine-melanin thin film formation was proposed based on the hydrophobicity of dopamine-melanin aggregates and the mass transport of the aggregates to the air/solution interface as a result of convective flow. The thickness of the interfacial films increased linearly with the dopamine concentration and the reaction time. The dopamine-melanin thin film and granules (formed in bulk liquid phase) with a double-layered structure were transferred onto a solid substrate to mimic the (keratin layer)/(melanin granules) structure present in bird plumage, thereby preparing full dopamine-melanin thin-film reflectors. The reflected color of the thin-film reflectors depended on the film thickness, which could be adjusted according to the dopamine concentration. The reflectance of the resulted reflectors exhibited a maximal reflectance value of 8-11%, comparable to that of bird plumage (â¼11%). This study provides a useful, simple, and low-cost approach to the fabrication of biomimetic thin-film reflectors using full dopamine-melanin materials.
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Materiales Biomiméticos/química , Melaninas/química , Nanotecnología/métodos , Soluciones Farmacéuticas/química , ColorRESUMEN
Methylmalonyl CoA mutase deficiency due to MUT gene defect has been known as the main cause of isolated methylmalonic acidemia in Mainland China. This study reported a patient with isolated methylmalonic aciduria (MUT type) characterized as acute brainstem encephalitis and myelitis. The previously healthy girl presented with fever, lethargy and progressive weakness in her extremities at the age of 3 years and 2 months. Three day later, she had respiratory distress and consciousness. Cranial MRI revealed bilateral symmetrical lesion of pallidum, brain stem and spinal cord, indicating acute brainstem encephalitis and myelitis. Her blood propionylcarnitine (6.83 µmol/L vs normal range 1.0 to 5.0 µmol/L) and urinary methylmalonic acid (133.22 mmol/mol creatinine vs normal range 0.2 to 3.6 mmol/mol creatinine) increased significantly. Plasma total homocysteine was normal. On her MUT gene, a reported mutation (c.1630_1631GG>TA) and a novel mutation (c.1663C>T, p.A555T) were identified, which confirmed the diagnosis of methylmalonic aciduria (MUT type). After cobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine, progressive improvement has been observed. The clinical manifestation of patients with methylmalonic aciduria is complex. Metabolic study and gene analysis are keys for the diagnosis and treatment of the disorder.
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Errores Innatos del Metabolismo de los Aminoácidos/etiología , Tronco Encefálico/patología , Encefalitis/etiología , Metilmalonil-CoA Mutasa/genética , Mutación , Mielitis/etiología , Enfermedad Aguda , Preescolar , Femenino , HumanosRESUMEN
cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine organic acids and genetic features of the patient were reported. The boy presented with fever, feeding difficulty and lethargy at the age of 2 months. Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis and liver damage. His blood propionylcarnitine and urinary methylmalonic acid levels increased significantly, but the plasma total homocysteine level was in the normal range, which supported the diagnosis of isolated methylmalonic aciduria. Gene analysis was performed by direct sequencing. No mutation in the MUT gene was found. However, a reported mutation c.577G>A (p.E193K) and a novel mutation c.562G>A (p.V188M) in the MMAB gene were identified, which confirmed the diagnosis of methylmalonic aciduria cblB type. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 3 years and 11 months old and has a normal development condition. The phenotypes of the patients with cblB defect are nonspecific. Metabolic analysis and MMAB gene analysis are keys for the diagnosis of the disorder.
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Transferasas Alquil y Aril/genética , Errores Innatos del Metabolismo de los Aminoácidos/genética , Mutación , Humanos , Lactante , MasculinoRESUMEN
Biomimetic polymer composites with water-active mechanically adaptive and shape-memory behaviour in different pH environments are synthesised by using chitosan-modified cellulose whiskers (CS-CWs) as the stimulus-responsive phase and thermoplastic polyurethane (TPU) as the resilient matrix. The effect of surface modification on the mechanically adaptive behaviour of CS-CW/TPU composites is investigated by using three representative solutions with various pH values. The results show that surface modification significantly enhances the modulus contrast under wet and dry conditions with the acidic solution as the stimulus, while maintaining the high modulus contrast with the basic solution as the stimulus. CS-CW/TPU composites also exhibit excellent shape-memory effects in all three solutions that are comparable to those pristine CW/TPU composites. Furthermore, activation of force generation in the stretched CS-CW/TPU composites by water absorption/desorption was observed.
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Celulosa/química , Quitosano/química , Elastómeros/química , Elastómeros/síntesis química , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Poliuretanos/química , Propiedades de Superficie , Agua/químicaRESUMEN
Biodegradable and biocompatible materials with shape-memory effects (SMEs) are attractive for use as minimally invasive medical devices. Nanocomposites with SMEs were prepared from biodegradable poly(glycerol sebacate urethane) (PGSU) and renewable cellulose nanocrystals (CNCs). The effects of CNC content on the structure, water absorption, and mechanical properties of the PGSU were studied. The water-responsive mechanically adaptive properties and shape-memory performance of PGSU-CNC nanocomposites were observed, which are dependent on the content of CNCs. The PGSU-CNC nanocomposite containing 23.2 vol % CNCs exhibited the best SMEs among the nanocomposites investigated, with the stable shape fixing and shape recovery ratios being 98 and 99%, respectively, attributable to the formation of a hydrophilic, yet strong, CNC network in the elastomeric matrix. In vitro degradation profiles of the nanocomposites were assessed with and without the presence of an enzyme.
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Materiales Biocompatibles/química , Celulosa/análogos & derivados , Celulosa/química , Poliuretanos/química , Implantes Absorbibles , Ácidos Decanoicos/química , Elasticidad , Glicerol/química , Interacciones Hidrofóbicas e Hidrofílicas , Lipasa/química , Nanocompuestos , Nanopartículas/química , Polímeros/química , Propiedades de Superficie , Resistencia a la TracciónRESUMEN
The design and synthesis of a novel series of potent gamma secretase modulators is described. Exploration of various spacer groups between the triazole ring and the aromatic appendix in 2 has led to anilinotriazole 28, which combined high in vitro and in vivo potency with an acceptable drug-like profile.
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Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Compuestos de Anilina/química , Triazoles/química , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina/síntesis química , Compuestos de Anilina/metabolismo , Animales , Encéfalo/metabolismo , Diseño de Fármacos , Humanos , Ratones , Ratones Transgénicos , Unión Proteica , Relación Estructura-Actividad , Triazoles/síntesis química , Triazoles/metabolismoRESUMEN
Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder. It is known that MTHFR deficiency may result in hyperhomocysteinemia, but MTHFR deficiency-induced schizophrenia has been rarely reported. Here we present the clinical course, biochemical and genetic characteristics of schizophrenia resulted from MTHFR deficiency in a school-age boy. He was 13 years old. He was admitted with a two-year history of fear, auditory hallucination, learning difficulty, sleeping problems, irascibility, drowsing and giggling. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Further DNA sequencing analysis showed 665C>T homozygous mutations in the MTHFR gene. The patient was diagnosed with MTHFR deficiency-associated schizophrenia and treatment with calcium folinate, vitamin B12, vitamin B6, and betaine was initiated. After the treatment for 1 week, his plasma and urine levels of homocysteine were decreased to a normal range and the clinical symptoms were significantly improved. After 3 months of treatment, the patient returned to school. He is now living with normal school life. In summary, children with late-onset MTHFR deficiency and secondary cerebral folate deficiency may lead to schizophrenia. This rare condition can be early diagnosed through analyses of blood and urine total homocysteine, amino acids in blood and folate in blood and cerebral fluid and successfully treated with folinic acid, vitamin B6, vitamin B12 and betaine.
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Homocistinuria/complicaciones , Metilenotetrahidrofolato Reductasa (NADPH2)/deficiencia , Espasticidad Muscular/complicaciones , Esquizofrenia/etiología , Adolescente , Secuencia de Bases , Homocistinuria/diagnóstico , Homocistinuria/tratamiento farmacológico , Humanos , Masculino , Datos de Secuencia Molecular , Espasticidad Muscular/diagnóstico , Espasticidad Muscular/tratamiento farmacológico , Trastornos Psicóticos/complicaciones , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development confirmed the prenatal diagnosis.
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Adenosina Trifosfatasas/genética , Proteínas de Transporte de Catión/genética , Síndrome del Pelo Ensortijado/genética , Diagnóstico Prenatal , ATPasas Transportadoras de Cobre , Humanos , Lactante , Masculino , Síndrome del Pelo Ensortijado/diagnóstico , MutaciónRESUMEN
Developing stable room-temperature phosphorescence (RTP) emission without being affected by moisture and mechanical force remains a great challenge for purely organic systems, due to their triplet states sensitive to the infinitesimal motion of phosphors and the oxygen quencher. We report a kind of highly robust phosphorescent systems, by doping a rigid phosphor into a copolymer (polyvinyl butyral resin) matrix with a balance of mutually exclusive features, including a rigidly hydrophilic hydrogen bond network and elastically hydrophobic constituent. Impressively, these RTP polymeric films have superior adhesive ability on various surfaces and showed reversible photoactivated RTP with lifetimes up to 5.82 seconds, which can be used as in situ modulated anticounterfeit labels. They can maintain a bright afterglow for over 25.0 seconds under various practical conditions, such as storage in refrigerators, soaking in natural water for a month, or even being subjected to strong collisions and impacts. These findings provide deep insights for developing stable ultralong RTP materials with desirable comprehensive performance.
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BACKGROUND: Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. RESULTS: Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. CONCLUSIONS: Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.
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Anomalías Múltiples , Errores Innatos del Metabolismo de los Aminoácidos , Síndrome de Angelman , Citrulinemia , Masculino , Femenino , Humanos , Niño , Proteínas de Transporte de Membrana MitocondrialRESUMEN
Picolitre monodisperse droplet printing technology has important applications in biochemistry, such as accounting for quantitative analysis and single-cell analysis, and can be used for parallel high-throughput analysis of biomarkers and chemicals. However, commonly used droplet generation devices require complex control systems or customised microfluidic chips, making them costly and difficult for researchers to operate. Additionally, generating picolitre monodisperse droplets with microfluidic devices necessitates the introduction of an oil phase to block and separate the liquid. This requirement can reduce the throughput of the target droplets and cause cell contamination, hindering the adoption of this technology. By employing a common 1-mm-diameter capillary in the laboratory in combination with a piezoelectric transducer, we have achieved on-demand picolitre droplet printing of less than 100 pL in an oil-free environment. The device was found to be biocompatible with K562 cells. This approach is less costly, offers greater operational freedom, and is easier to integrate with other downstream assay modules or even handheld cell-printing devices. This study holds great potential for application in areas such as single-cell analysis, cell sampling, and pharmaceutical analysis.
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Dispositivos Laboratorio en un Chip , Humanos , Células K562 , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Análisis de la Célula Individual/métodos , Diseño de EquipoRESUMEN
The evolution of amide 3 into conformationally restricted bicyclic triazolo-piperidine 14-S as a γ-secretase modulator is described. This is a potential disease modifying anti-Alzheimer's drug which demonstrated high in vitro and in vivo potency against Aß42 peptide, reduced lipophilicity and enhanced brain free fraction compared to the previous series.
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Enfermedad de Alzheimer/enzimología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Diseño de Fármacos , Piperidinas/farmacología , Triazoles/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/metabolismo , Perros , Humanos , Ratones , Microsomas Hepáticos/metabolismo , Modelos Moleculares , Piperidinas/química , Piperidinas/metabolismo , Triazoles/química , Triazoles/metabolismoRESUMEN
Fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of α-galactosidase A (GLA). Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction. Patients of severe cases die young. It has been proved that enzyme replacement therapy is a useful method to treat patients with Fabry disease. But the clinical diagnosis of the patients may often be difficult because of the lack of specific symptoms. In this study, a Chinese boy was diagnosed as Fabry disease at the age of 11 years with episodic pain for 7 years. The boy described the onset, at the age of 4 years, of episodic burning pain in the toes. Generalized aching and pain in the feet became progressive in the past two years and his hands were also affected. Divers analgesics were tried without effects. When he was admitted at the age of 11 years, none of complications was found in his heart, brain, kidneys, skin and eyes by routine laboratory examinations. Significantly decreased GLA activity of peripheral leucocytes [1.0 nmol/(h×mg protein) vs. normal control 24.5 to 86.1 nmol/(h×mg protein)] supported the diagnosis of Fabry disease. A splicing mutation IVS6+2 T>C was identified on his GLA gene. But it was not found in his mother and younger sister. The incidence of Fabry disease is not clear in Mainland China. The patients usually have insidious onset with complex and non-specific clinical manifestations. Stroke, uremia, cardiomyopathy and multiple organ dysfunctions are common at the late stage. Early diagnosis is the key point to reduce the mortality and handicap. GLA enzyme activity is important to the diagnosis of Fabry disease. The mutation analysis of GLA gene is helpful for genetic counseling.
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Edad de Inicio , Enfermedad de Fabry/diagnóstico , Niño , Preescolar , Terapia de Reemplazo Enzimático , Humanos , Masculino , Mutación , Neuralgia/etiología , alfa-Galactosidasa/genéticaRESUMEN
OBJECTIVE: To investigate the phenotype and genotype of a Chinese boy and his family affected by infantile Sandhoff disease. METHODS: The proband, a boy, was the first child born to a non-consanguineous couple. He showed startle reaction after birth and progressive psychomotor regression from the age of 8 months. From the age of 16 months, he presented seizures. When he was admitted at 17 months old, severe mental retardation and weakness were observed. Fundus examination revealed bilateral cherry-red spots in the macula and optic atrophy. Cranial MRI revealed abnormal signals in the thalamus, basal ganglia and white matter. Enzymatic assay and genetic testing were performed for the diagnosis. His mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene diagnosis to the fetus was performed by direct sequencing. RESULTS: Significant deficient total ß-hexosaminidase (A and B) activity in peripheral leucocytes of the patient (0.0 nmol/h/mg compared with normal control, 41.9 to 135.1 nmol/h/mg) supported the diagnosis of Sandhoff disease. On his HEXB gene, two mutations were found. c.1645G-A (p.G549R) was novel. c.IVS7-48T was a reported mutation. Now, the patient was 2 years and 3 months old, with progressive general failure, severe epilepsy, blindness and hypermyotonia. Subsequently, the mother visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene analysis of the amniocytes was performed by direct sequencing. Both of the two mutations were not detected from cultured amniocytes. The result revealed that the fetus was not affected by Sandhoff disease. A healthy girl, the sibling of the proband, was born in term. Postnatal enzyme analysis and genetic analysis of the cord blood cells confirmed the prenatal diagnosis. CONCLUSION: One novel mutation on HEXB gene was identified. Prenatal diagnosis to the fetus of this family was performed by amniocytes gene analysis.
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Diagnóstico Prenatal , Enfermedad de Sandhoff/diagnóstico , Enfermedad de Sandhoff/genética , Cadena beta de beta-Hexosaminidasa/genética , Adulto , Líquido Amniótico/citología , Preescolar , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Humanos , Masculino , Mutación , EmbarazoRESUMEN
Argininemia is a rare, autosomal recessive, metabolic disorder caused by an hereditary deficiency of hepatocytes arginase due to ARG1 gene defect. Arginase is the final enzyme in the urea cycle, catalyzing the hydrolysis of arginine to ornithine and urea. Research advances in the clinical manifestations, diagnosis, treatment, prenatal diagnosis and genetics of argininemia were reviewed in this paper. The clinical manifestations of patients with argininemia are complicated and nonspecific so that clinical diagnosis is usually difficult and delayed. Progressive spastic tetraplegia, seizures and cerebella atrophy are common clinical features of the disease. Blood amino acids analysis, arginase assay and ARG1 gene analysis are important to the diagnosis of argininemia. Early diagnosis and a protein-restricted diet with citrulline and benzoate supplements can contribute a lot to improve patient prognosis. With the application of liquid chromatography-tandem mass spectrometry in selective screening and newborn screening for inborn errors of metabolism, an ever-increasing number of patients with argininemia are detected at the asymptomatic or early stages.