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Tryptophan hydroxylase 1 (TPH1) has emerged as a target for the treatment of metabolic diseases including obesity and fatty liver disease. A series of xanthine derivatives were synthesized and evaluated for their TPH1 inhibition. Among the synthesized compounds, compound 40 showed good in vitro activity and liver microsomal stability. Docking studies revealed that compound 40 showed better binding to TPH1 via key intermolecular interactions involving the xanthine scaffold, imidazo-thiazolyl ring, and hydroxyl-containing phenacyl moiety. In addition, compound 40 effectively suppressed the adipocyte differentiation of 3 T3-L1 cells.
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Alcaloides , Hepatopatia Gordurosa não Alcoólica , Humanos , Diuréticos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Triptofano Hidroxilase/antagonistas & inibidores , Xantinas/química , Xantinas/farmacologiaRESUMO
Microplastics, small pieces of plastic derived from polystyrene, have recently become an ecological hazard due to their toxicity and widespread occurrence in aquatic ecosystems. In this study, we exposed zebrafish larvae to two types of fluorescent polystyrene nanoparticles (PS-NPs) to identify their size-dependent effects. PS-NPs of 50 nm, unlike 100 nm PS-NPs, were found to circulate in the blood vessels and accumulate in the brains of zebrafish larvae. Behavioral and electroencephalogram (EEG) analysis showed that 50 nm PS-NPs induce abnormal behavioral patterns and changes in EEG power spectral densities in zebrafish larvae. In addition, the quantification of endogenous neurochemicals in zebrafish larvae showed that 50 nm PS-NPs disturb dopaminergic metabolites, whereas 100 nm PS-NPs do not. Finally, we assessed the effect of PS-NPs on the permeability of the blood-brain barrier (BBB) using a microfluidic system. The results revealed that 50 nm PS-NPs have high BBB penetration compared with 100 nm PS-NPs. Taken together, we concluded that small nanoparticles disturb the nervous system, especially dopaminergic metabolites.
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Nanopartículas , Poluentes Químicos da Água , Animais , Ecossistema , Larva/metabolismo , Microplásticos/toxicidade , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Plásticos/metabolismo , Poliestirenos/farmacologia , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismoRESUMO
Infection with pathogens activates the endothelial cell and its sustained activation may result in impaired endothelial function. Endothelial dysfunction contributes to the pathologic angiogenesis that is characteristic of infection-induced inflammatory pathway activation. Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a protein receptor which recognizes bacterial molecules and stimulates an immune reaction in various cells; however, the underlying molecular mechanisms in the regulation of inflammation-triggered angiogenesis are not fully understood. Here we report that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated miR-125a serves as an important regulator of NOD1 agonist-mediated angiogenesis in endothelial cells by directly targeting NOD1. Treatment of human umbilical vein endothelial cells with natural PPARγ ligand, 15-Deoxy-Delta12,14-prostaglandin J2, led to inhibition of NOD1 expression; contrarily, protein levels of NOD1 were significantly increased by PPARγ knockdown. We report that PPARγ regulation of NOD1 expression is a novel microRNA-mediated regulation in endothelial cells. MiR-125a expression was markedly decreased in human umbilical vein endothelial cells subjected to PPARγ knockdown while 15-Deoxy-Delta12,14-prostaglandin J2 treatment increased the level of miR-125a. In addition, NOD1 is closely regulated by miR-125a, which directly targets the 3' untranslated region of NOD1. Moreover, both overexpression of miR-125a and PPARγ activation led to inhibition of NOD1 agonist-induced tube formation in endothelial cells. Finally, NOD1 agonist increased the formation of cranial and subintestinal vessel plexus in zebrafish, and this effect was abrogated by concurrent PPARγ activation. Overall, these findings identify a PPARγ-miR-125a-NOD1 signaling axis in endothelial cells that is critical in the regulation of inflammation-mediated angiogenesis.
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Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Neovascularização Patológica/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , PPAR gama/metabolismo , Vasculite/metabolismo , Animais , Células Cultivadas , Regulação para Baixo , Células Endoteliais/patologia , Humanos , Neovascularização Patológica/patologia , Vasculite/patologia , Peixe-ZebraRESUMO
It is well known that patients with peripheral neuropathy along with autonomic involvement can also exhibit autonomic hyperactivity. There are rare cases in which these patients developed posterior reversible encephalopathy syndrome (PRES). Patients with primary Sjögren's syndrome (pSS) may be more likely to exhibit autonomic hypofunction rather than autonomic hyperfunction, which is a rare event. In the present work, we report the first known case of PRES as an initial neurological manifestation of pSS.
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Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
In this study, 1-bromohexyl-1methylpiperidinium bromide (Br-6-MPRD) ionic liquid grafted quaternized chitosan (QCS) and polyvinyl alcohol (PVA) blends were composited with glycidyl trimethyl ammonium chloride (GTMAC) quaternized silica (QSiO2) at different dosages. Glutaraldehyde (GA) crosslinked the membranes and then processed into hydroxide form with an aqueous potassium hydroxide solution. The resultant IL-QCS/PVA/QSiO2 membranes exhibit significantly improved ionic conductivity, moderate water absorption and swelling ratio compared with the pristine IL-QCS/PVA anion exchange membrane (AEM). Among them, the hydroxide ion conductivity and power density of IL-QCS/PVA/QSiO2-7 membrane can reach up to 78 mS cm-1 at 80 °C and 115 mW cm-2 at 60 °C respectively. In addition, IL-QCS/PVA/QSiO2 membranes have excellent thermal, mechanical, and chemical stabilities, which can meet the application requirements of AEM for fuel cells.
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Compostos de Amônio , Quitosana , Hidróxidos , Líquidos Iônicos , Metacrilatos , Álcool de Polivinil , Polímeros , Ânions , Eletrólitos , Dióxido de SilícioRESUMO
The blood-brain-barrier (BBB) is made up of blood vessels whose permeability enables the passage of some compounds. A predictive model of BBB permeability is important in the early stages of drug development. The predicted BBB permeabilities of drugs have been confirmed using a variety of in vitro methods to reduce the quantities of drug candidates needed in preclinical and clinical trials. Most prior studies have relied on animal or cell-culture models, which do not fully recapitulate the human BBB. The development of microfluidic models of human-derived BBB cells could address this issue. We analyzed a model for predicting BBB permeability using the Emulate BBB-on-a-chip machine. Ten compounds were evaluated, and their permeabilities were estimated. Our study demonstrated that the permeability trends of ten compounds in our microfluidic-based system resembled those observed in previous animal and cell-based experiments. Furthermore, we established a general correlation between the partition coefficient (Kp) and the apparent permeability (Papp). In conclusion, we introduced a new paradigm for predicting BBB permeability using microfluidic-based systems.
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Mice are the premier mammalian models for studies of human physiology and disease, bearing extensive biological similarity to humans with far fewer ethical, economic, or logistic complications. To facilitate glycomic studies based on the mouse model, we comprehensively profiled the mouse serum N-glycome using isomer-specific nano-LC/MS and -LC/MS/MS. N-Glycans were identified by accurate mass MS and structurally elucidated by MS/MS. Porous graphitized carbon nano-LC was able to separate out nearly 300 N-linked glycan compounds (including isomers) from just over 100 distinct N-linked glycan compositions. Additional MS/MS structural analysis was performed on a number of novel N-glycans, revealing the structural characteristics of modifications such as dehydration, O-acetylation, and lactylation. Experimental findings were combined with known glycobiology to generate a theoretical library of all biologically possible mouse serum N-glycan compositions. The library may be used for automated identification of complex mixtures of mouse N-glycans, with possible applications to a wide range of mouse-related research endeavors, including pharmaceutical drug development and biomarker discovery.
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Polissacarídeos/sangue , Animais , Cromatografia Líquida , Feminino , Espectrometria de Massas , Camundongos , Camundongos Transgênicos , EstereoisomerismoRESUMO
Patients with galactosemia accumulate galactose in their bodies, requiring a lifelong galactose-restricted diet. Therefore, accurate information on the galactose content in commercial agro-food resources is essential. The HPLC method generally used for sugar analysis has low separation and detection sensitivity. Here, we sought to establish an accurate analytical method for determining the galactose content in commercial agro-food resources. To that aim, we employed gas chromatography with flame-ionization detection to detect trimethylsilyl-oxime (TMSO) sugar derivatives (concentration: ≤0.1 mg/100 g). The galactose content in 107 Korean agro-food resources reflecting intake patterns was then analyzed. The galactose content in steamed barley rice was 5.6 mg/100 g, which was higher than that in steamed non-glutinous and glutinous rice. Moist-type and dry-type sweet potatoes, blanched zucchini, and steamed Kabocha squash had high galactose content (36.0, 12.8, 23.1, and 61.6 mg/100 g, respectively). Therefore, these foods are detrimental to patients with galactosemia. Among fruits, avocado, blueberry, kiwi, golden kiwifruit, and sweet persimmon had galactose contents of ≥10 mg/100 g. Dried persimmon had 132.1 mg/100 g and should therefore be avoided. Mushrooms, meat, and aquatic products showed low galactose content (≤10 mg/100 g), making them safe. These findings will help patients to manage their dietary galactose intake.
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Background: Polymyositis (PM) and dermatomyositis (DM) are two distinct subgroups of idiopathic inflammatory myopathies. Dysferlinopathy, caused by a dysferlin gene mutation, usually presents in late adolescence with muscle weakness, degenerative muscle changes are often accompanied by inflammatory infiltrates, often resulting in a misdiagnosis as polymyositis. Objective: To identify differential biological pathways and hub genes related to polymyositis, dermatomyositis and dysferlinopathy using bioinformatics analysis for understanding the pathomechanisms and providing guidance for therapy development. Methods: We analyzed intramuscular ribonucleic acid (RNA) sequencing data from seven dermatomyositis, eight polymyositis, eight dysferlinopathy and five control subjects. Differentially expressed genes (DEGs) were identified by using DESeq2. Enrichment analyses were performed to understand the functions and enriched pathways of DEGs. A protein-protein interaction (PPI) network was constructed, and clarified the gene cluster using the molecular complex detection tool (MCODE) analysis to identify hub genes. Results: A total of 1,048, 179 and 3,807 DEGs were detected in DM, PM and dysferlinopathy, respectively. Enrichment analyses revealed that upregulated DEGs were involved in type 1 interferon (IFN1) signaling pathway in DM, antigen processing and presentation of peptide antigen in PM, and cellular response to stimuli in dysferlinopathy. The PPI network and MCODE cluster identified 23 genes related to type 1 interferon signaling pathway in DM, 4 genes (PDIA3, HLA-C, B2M, and TAP1) related to MHC class 1 formation and quality control in PM, and 7 genes (HSPA9, RPTOR, MTOR, LAMTOR1, LAMTOR5, ATP6V0D1, and ATP6V0B) related to cellular response to stress in dysferliniopathy. Conclusion: Overexpression of genes related to the IFN1 signaling pathway and major histocompatibility complex (MHC) class I formation was identified in DM and PM, respectively. In dysferlinopathy, overexpression of HSPA9 and the mTORC1 signaling pathway genes was detected.
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PURPOSE: This study aimed to investigate the incidence of myotonic dystrophy type 1 (DM1) and the status of multi-organ involvement. METHODS: This was a nationwide, population-based, cohort study using data from the Korean National Health Claims database. All patients with DM1 from the entire population aged ≤ 80 years were included. To identify possible systemic diseases along with DM1, we searched for concurrent codes for systemic diseases. To assess the recent status of systemic evaluation, concurrent codes for various diagnostic and treatment modalities were collected. Cumulative incidence during 2016-2019 was first evaluated then systemic evaluation for those patients was assessed during 2010-2019. RESULTS: A total of 387 patients (47.8% men) during the recent 4-year study period (2016-2019) were diagnosed with DM1. The cumulative incidence in the general population was 0.77 (95% confidence interval: 0.76-0.77) per 100,000 persons. In newly developed incidental cases, cardiac involvement developed in 51.2%, pneumonia in 30.7%, diabetes in 26.9%, brain involvement in 18.1%, cataract in 13.7%, and cancers in 5.4% of total patients. Electrocardiography was performed in 93.8%, Holter in 33.9%, and echocardiography in 31.3% of the total patients for cardiac evaluation. CONCLUSIONS: The incidence estimates of DM1 in the Asian population were lower than those of Caucasians. This study provides the real situation of screening and treatment for systemic diseases related to DM1. These detailed estimates could promote an understanding of the current disease status and allow for appropriate planning within the healthcare system.
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Distrofia Miotônica , Estudos de Coortes , Eletrocardiografia , Feminino , Coração , Humanos , Incidência , Masculino , Distrofia Miotônica/epidemiologia , Distrofia Miotônica/terapiaRESUMO
Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. Although WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed on the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment.
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OBJECTIVE: Electrooculography (EOG) records eyeball movements as changes in the potential difference between the negatively charged retina and the positively charged cornea. We aimed to investigate whether reliable EOG waveforms can be evoked by electrical stimulation of the oculomotor and abducens nerves during skull base surgery. METHODS: We retrospectively reviewed the records of 18 patients who had undergone a skull base tumor surgery using EOG (11 craniotomies and seven endonasal endoscopic surgeries). Stimulation was performed at 5 Hz with a stimulus duration of 200 µs and an intensity of 0.1-5 mA using a concentric bipolar probe. Recording electrodes were placed on the upper (active) and lower (reference) eyelids, and on the outer corners of both eyes; the active electrode was placed on the contralateral side. RESULTS: Reproducibly triggered EOG waveforms were observed in all cases. Electrical stimulation of cranial nerves (CNs) III and VI elicited positive waveforms and negative waveforms, respectively, in the horizontal recording. The median latencies were 3.1 and 0.5 ms for craniotomies and endonasal endoscopic surgeries, respectively (p=0.007). Additionally, the median amplitudes were 33.7 and 46.4 µV for craniotomies and endonasal endoscopic surgeries, respectively (p=0.40). CONCLUSION: This study showed reliably triggered EOG waveforms with stimulation of CNs III and VI during skull base surgery. The latency was different according to the point of stimulation and thus predictable. As EOG is noninvasive and relatively easy to perform, it can be used to identify the ocular motor nerves during surgeries as an alternative of electromyography.
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BACKGROUND AND PURPOSE: This study was designed to investigate clinical and pathologic characteristics of five Korean patients with RYR1-related congenital myopathy (CM). METHODS: Five patients from unrelated families were diagnosed with RYR1-related CM via direct or targeted sequencing of RYR1. Their clinical, mutational, and pathologic findings were then analyzed. RESULTS: Seven different mutations were identified, including two novel mutations: c.5915A>T and c.12250C>T. All of the patients presented at infancy with proximal dominant weakness and delayed motor milestones. Other clinical findings were scoliosis in three patients, winged scapula in two, hip dislocation in one, and pectus excavatum in one. Ophthalmoplegia was observed in one patient with a novel recessive mutation. Two of three muscle specimens revealed a myopathic pattern with core. CONCLUSIONS: We have identified a novel compound heterozygous RYR1 mutation and demonstrated clinical and pathologic findings in five Korean patients with RYR1-related CM.
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BACKGROUND AND PURPOSE: Neurolymphomatosis is a rare manifestation of hematological malignancy and is characterized by direct infiltration of the peripheral nervous system. The objective of this study was to identify the clinical and electrophysiological features of neurolymphomatosis. METHODS: We retrospectively analyzed the medical records of 13 patients with neurolymphomatosis. Seven (54%) of the patients were men, and the median age at symptom onset was 60.0 years. RESULTS: The most common type of underlying malignancy was diffuse large B-cell lymphoma (69%). Twelve patients had painful asymmetric neuropathies. The median survival time after diagnosis was 7 months, and 12 patients died during the study period. Thirty-eight motor nerve conduction studies (NCSs) were performed in the affected nerves. Ten and 28 motor nerves were classified into the conduction-block and simple-axon-degeneration groups, respectively. The median time interval between symptom onset and the NCS was significantly shorter in the conduction-block group than in the simple-axon-degeneration group (p=0.032). However, no significant differences in the motor nerve conduction velocities, terminal latencies, and distal compound muscle action potential amplitudes were identified between the conduction-block and simple-axon-degeneration groups. The conduction-block group showed excessive temporal dispersion in only five of the ten NCSs (50%). Follow-up NCSs revealed that partial conduction blocks had changed into axonal degeneration patterns. CONCLUSIONS: This is the first study to analyze the electrophysiological features of patients with neurolymphomatosis. Our findings showed that a partial conduction block is not rare and is an early nerve conduction abnormality in neurolymphomatosis.
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Hyperkalemic periodic paralysis (hyperKPP) is a muscle channelopathy characterized by recurrent paralytic attacks. Our previous study, in which we conducted whole-body muscle magnetic resonance imaging (MRI) in patients with hyperKPP, revealed muscle atrophy and fatty change in the lower extremity, especially in older persons. The aim of current study was to identify the progression of myopathy in hyperKPP patients had been assessed in the previous study. We performed lower-extremity muscle MRI in seven hyperKPP patients carrying the T704M mutation in the SCN4A gene at an interval of 30 months. Muscle atrophy, edematous change, fatty change, and fat fraction quantified using the Dixon technique were compared with the previous MRI findings. The lower-extremity MRI scan showed progressive muscle pathologic findings when compared with the previous study. Muscle atrophy, edematous change, and fatty change were prominent in the superficial posterior compartment of the lower leg. The follow-up lower-extremity muscle MRI findings provide evidence for chronic progressive myopathy and suggest the usefulness of MRI for assessing disease progression in patients with hyperKPP. This study is meaningful in terms of providing data showing the longitudinal changes of muscles in patients with periodic paralysis.
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Imageamento por Ressonância Magnética , Músculo Esquelético/diagnóstico por imagem , Mutação , Canal de Sódio Disparado por Voltagem NAV1.4/genética , Paralisia Periódica Hiperpotassêmica/diagnóstico por imagem , Paralisia Periódica Hiperpotassêmica/genética , Tecido Adiposo/diagnóstico por imagem , Adolescente , Adulto , Atrofia , Progressão da Doença , Família , Feminino , Seguimentos , Humanos , Extremidade Inferior/diagnóstico por imagem , Masculino , Força Muscular , Músculo Esquelético/patologia , Fenótipo , Adulto JovemRESUMO
Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a central role in promoting vascular inflammatory response; however, the molecular mechanism underlying this component of inflammation and angiogenesis is not fully understood. Here we report a novel microRNA mediated suppression of endothelial CD40 expression. We found that CD40 is closely regulated by miR-424 and miR-503, which directly target its 3' untranslated region. Pro-inflammatory stimuli led to increased endothelial CD40 expression, at least in part due to decreased miR-424 and miR-503 expression. In addition, miR-424 and miR-503 reduced LPS induced EC sprouting, migration and tube formation. Moreover, we found that miR-424 and miR-503 expression is directly regulated by peroxisome proliferator-activated receptor gamma (PPARγ), whose endothelial expression and activity are decreased in response to inflammatory factors. Finally, we demonstrate that mice with endothelial-specific deletion of miR-322 (miR-424 ortholog) and miR-503 have augmented angiogenic response to LPS in a Matrigel plug assay. Overall, these studies identify a PPARγ-dependent miR-424/503-CD40 signaling axis that is critical for regulation of inflammation mediated angiogenesis.
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Antígenos CD40/genética , Inflamação/genética , Neovascularização Patológica/genética , PPAR gama/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Camundongos , MicroRNAs/genética , Morfogênese/genética , Transdução de SinaisRESUMO
Myasthenia gravis (MG)(1) is an autoimmune disease directed at the neuromuscular junction, and cytokines are thought to contribute to its immunopathogenesis. Interleukin-27 (IL-27)(2) plays a complex and pleiotropic role in immune responses associated with T helper cells. To assess the role of IL-27 in MG, we determined serum IL-27 levels in MG patients (n=32) compared to healthy controls (n=50). The median serum IL-27 level was significantly higher in MG patients (35.947pg/mL) than in controls (19.885pg/mL). Furthermore, serum IL-27 was significantly higher in early onset MG. This study suggests the possibility that IL-27 might contribute to MG pathogenesis or immunoregulation.
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Interleucinas/sangue , Miastenia Gravis/sangue , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Erythropoietin is a therapeutic glycoprotein that stimulates red blood cell production. The quality, safety and potency of recombinant erythropoietins are determined largely by their glycosylation. Small variations in cell culture conditions can significantly affect the glycosylation, and therefore the efficacy, of recombinant erythropoietins. Thus, detailed glycomic analyses are necessary to assess biotherapeutic quality. We have developed a platform for qualitative and quantitative glycomic analysis of recombinant erythropoietins. RESULTS: The platform was used to profile native N-glycans from three production batches of darbepoetin alfa (also known as NESP), a common form of recombinant erythropoietin. Darbepoetin alfa was found to contain an abundance of large, multi-antennary N-glycans with high levels of sialylation, O-acetylation and dehydration. Results were verified by independent orthogonal analysis with both MALDI-TOF and nano-LC/Q-TOF MS. CONCLUSION: This platform may be applied to QC and batch analysis of not only recombinant erythropoietin, but also other complex, glycosylated biotherapeutics and biosimilars.
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Medicamentos Biossimilares/análise , Eritropoetina/análise , Polissacarídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Medicamentos Biossimilares/normas , Configuração de Carboidratos , Eritropoetina/genética , Eritropoetina/normas , Glicosilação , Humanos , Isomerismo , Nanotecnologia , Ácidos Neuramínicos/análise , Peptídeo-N4-(N-acetil-beta-glucosaminil) Asparagina Amidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/normas , Controle de Qualidade , Proteínas Recombinantes/análise , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/normas , Extração em Fase Sólida , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normasRESUMO
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive multiorgan disease, frequently associated with mutations in the thymidine phosphorylase (TYMP) gene. TYMP encodes thymidine phosphorylase (TP), which has an essential role in the nucleotide salvage pathway for mitochondrial DNA (mtDNA) replication. This study reports an MNGIE patient with novel compound heterozygous missense mutations (Thr151Pro and Leu270Pro) in TYMP. Each mutation was inherited from one parent. Neither mutation was found in the controls and the mutation sites were well conserved between different species. Neither large deletion nor causative point mutations were found in the mtDNA. The patient presented with MNGIE symptoms, including gastrointestinal discomfort, external ophthalmoplegia, pigmentary retinopathy and demyelinating type diffuse sensory motor polyneuropathy. The patient demonstrated an early-onset but mild phenotype, with 9.6% TP activity; therefore, patients with these compound heterozygous mutations may exhibit a mild phenotype with a variable onset age according to TP activity level.