AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the C...AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.展开更多
Hereditary angioedema secondary to C1-inhibitor deficiency is a rare autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor.An eight-year-old girl showed periorbital painless swelling, diag...Hereditary angioedema secondary to C1-inhibitor deficiency is a rare autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor.An eight-year-old girl showed periorbital painless swelling, diagnosed as ethmoiditis. A craniofacial scan did not evidence a paranasal sinus involvement, C1INH levels were undetectable, with low C4 levels: 7.6 mg/dl and C1INH: <8.46 mg/dl. The genetic study identified a rare mutation of the C1INH gene. This clinical report is of relieve because paediatric cases described in literature are rare, did not presented a positive family history, and received a diagnosis after many attacks. Furthermore our girl received a prompt diagnosis of HAE at the first attack of angioedema.展开更多
A pregnant woman diagnosed with type 1 angioedema seeks care at a public hospital for planning the delivery. This report presents ways to prevent and manage an acute HAE crisis during childbirth and early postpartum w...A pregnant woman diagnosed with type 1 angioedema seeks care at a public hospital for planning the delivery. This report presents ways to prevent and manage an acute HAE crisis during childbirth and early postpartum without the availability of first-line medications, such as plasma-derived human C1-INH concentrate.展开更多
BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatit...BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation.展开更多
Abdominal involvement in angioedema is often a challenge to diagnose.Acute onset abdominal pain is its most common presenting symptom,and misdiagnosis may lead to unnecessary surgical intervention.Familiarity with the...Abdominal involvement in angioedema is often a challenge to diagnose.Acute onset abdominal pain is its most common presenting symptom,and misdiagnosis may lead to unnecessary surgical intervention.Familiarity with the types and presentations of angioedema can be invaluable to clinicians as they consider the differential diagnoses of a patient presenting with abdominal pain. Detailed personal and family histories,careful physical examination of the patient,combined with knowledge of angioedema types,can help clinicians perform their diagnostic evaluation.An accurate diagnosis is essential in order to provide appropriate treatment to patients with angioedema.Depending upon the diagnosis,treatment may be the avoidance of provoking factors(such as allergens or medications),inhibiting histamine-provoked reactions,or treating C1 esterase inhibitor deficiency.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong><em>Background:</em></strong> Very limited data are available regarding the associat...<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong><em>Background:</em></strong> Very limited data are available regarding the association of vitamin D with glycemic status among adults with newly detected type 2 diabetes mellitus (T2DM) in Bangladesh. <strong><em>Objectives:</em></strong> To determine vitamin D status and its association with glycemic status in Bangladeshi adults with newly detected T2DM. <strong><em>Materials and Methods:</em></strong> This cross-sectional study was carried out in 102 newly detected T2DM diagnosed on the basis of the American Diabetes Association 2017 criteria (age: 42.95 ± 10.68 yrs.;m/f: 44/58) and equal number of age and sex matched controls (age: 40.43 ± 11.04 years) recruited consecutively from the Department of Endocrinology, B中央人民政府 to measure serum vitamin D by high performance liquid chromatography method. <strong><em>Results:</em></strong> Both vitamin D deficiency (<20 ng/ml) (87.3% vs. 74.5%, <em>p </em>< 0.03) and severe vitamin D deficiency (<10 ng/ml) (56.2% vs. 26.3%, <em>p</em> < 0.001) were significantly higher in people with T2DM than control population. The mean level of 25(OH)D was significantly lower in adults with T2DM than control population (12.41 ± 6.85 ng/ml vs. 15.74 ± 6.25 ng/ml, <em>p</em> < 0.001). A significant inverse correlation was observed between vitamin D & HbA<span style="white-space:nowrap;"><sub>1</sub></span>c (r = <span style="white-space:nowrap;">-</span>0.249, <em>p</em> = 0.011) in patients with T2DM. HbA<span style="white-space:nowrap;"><sub>1</sub></span>c was linearly associated with vitamin D (<em>β </em>= <span style="white-space:nowrap;">-</span>0.26, <em>p</em> = 0.009) and severe vitamin D deficiency by binary (OR = 1.37, <em>p</em> = 0.003) and multinomial logistic regression (HbA<span style="white-space:nowrap;"><sub>1</sub></span>c ≥ 10%: OR = 4.25, <em>p </em>= 0.04) in people with T2DM after adjustment for age and BMI. <strong>Conclusions:</strong> Severe vitamin D deficiency was positively associated with T2DM and inversely associated with HbA<span style="white-space:nowrap;"><sub>1</sub></span>c in patients with newly detected T2DM.</span> </div>展开更多
Hereditary angioedema is a rare but life-threatening disease, usually resulting from upper respiratory tract traumas and stress. In this case report, we present the management of a 14-year-old female patient who was d...Hereditary angioedema is a rare but life-threatening disease, usually resulting from upper respiratory tract traumas and stress. In this case report, we present the management of a 14-year-old female patient who was diagnosed with hereditary angioedema and scheduled to undergo transurethral resection of bladder (TURB) procedure for bladder tumor. She was on prophylactic danazol treatment and prior to the operation the dose of danazol was increased. On the day of the operation, patient was given C1-IHN concentrate and was sedated. In conclusion, hereditary angioedema is a rare disease in which multidisciplinary and aggressive approach during anesthesia would yield successful results.展开更多
Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can r...Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutation was identified in 6 （9.2%） patients. The genotypes of 52 patients remained unknown. Conclusions Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.展开更多
文摘AIM:To evaluate the association between alpha-1 antitrypsin deficiency(A1ATD) and hepatocellular carcinoma(HCC) in patients with end-stage liver disease(ESLD).METHODS:Patients with cirrhosis and ESLD referred to the Cleveland Clinic Foundation for liver transplantation between 2003 and 2014 were included in the study(N = 675). ESLD was defined as having histological features of cirrhosis and/or radiological evidence of cirrhosis in the context of portal hypertension(ascites,variceal bleeding,thrombocytopenia,or hepatic encephalopathy). A1 ATD was diagnosed using phenotype characterization(MZ or ZZ),liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules,or both. Patients with other causes of liver diseases such as hepatitis C virus(HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCC was diagnosed by using imaging modalities,biopsy findings,or explanted liver inspection. Follow-up time was defined as the number of years from the diagnosis of cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow up visit. The rate of HCC was assessed using time-tointerval analysis for interval censored data.RESULTS:This study included 675 patients. 7% of subjects had A1ATD(n = 47). Out of all subjects who did not have A1 ATD,46% had HCV,17% had alcoholic liver disease,19% had NASH and 18% had another primary diagnosis. Of the 47 subjects with A1 ATD,15 had a primary diagnosis of A1ATD(PI*ZZ phenotype and PAS+ globules),8 had a PI*MZ phenotype alone,14 had PAS+ alone,and 10 had both the PI*MZ phenotype and PAS+. Median follow-up time was 3.4(25th,75 th percentiles:1,5.2) years. The overall rate of hepatocellular carcinoma in all subjects was 29%(n = 199). In the A1 ATD group,the incidence rate of HCC was 8.5% compared to 31% in the group of patients with other causes of cirrhosis(P = 0.001). Patients with ESLD due to A1 ATD had the lowest yearly cumulative rate of hepatocellular carcinoma at 0.88% per year compared to 2.7% for those with HCV cirrhosis,1.5% in patients with NASH and 0.9% in alcohol-induced liver disease(P < 0.001).CONCLUSION:Within this group of patients with ESLD,there was no significant association between A1 ATD and increased risk of HCC.
文摘Hereditary angioedema secondary to C1-inhibitor deficiency is a rare autosomal dominant disorder characterized by a deficiency of C1 esterase inhibitor.An eight-year-old girl showed periorbital painless swelling, diagnosed as ethmoiditis. A craniofacial scan did not evidence a paranasal sinus involvement, C1INH levels were undetectable, with low C4 levels: 7.6 mg/dl and C1INH: <8.46 mg/dl. The genetic study identified a rare mutation of the C1INH gene. This clinical report is of relieve because paediatric cases described in literature are rare, did not presented a positive family history, and received a diagnosis after many attacks. Furthermore our girl received a prompt diagnosis of HAE at the first attack of angioedema.
文摘A pregnant woman diagnosed with type 1 angioedema seeks care at a public hospital for planning the delivery. This report presents ways to prevent and manage an acute HAE crisis during childbirth and early postpartum without the availability of first-line medications, such as plasma-derived human C1-INH concentrate.
基金National Institutes of Health Grant,No.R01CA172086Plan Nacional of I+D,No.SAF2017-88041-R+5 种基金Ministerio de Economía y Competitividad de España,No.SAF2017-87301-RAsociación Española contra el Cáncer,No.AECC17/302Ayudas Fundación BBVA a equipos de Investigación Científica 2018Fondo Europeo de Desarrollo Regional,Ministerio de Economia y Competitividad de España,No.PGC2018-099857-BI00Basque Government Grants,No.IT1264-19Ministerio de Economia y Competitividad de España for the Severo Ochoa Excellence Accreditation,No.SEV-2016-0644.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘BACKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-CoA desaturase 1(SCD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1MCD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13C-uniformly labeled glucose.For the in vivo part of the study,male C57BL/6J mice were randomly fed a control or 0.1MCD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS Combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORC1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PACCα/β(S79),SCD1,CPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQCRC2),tricarboxylic acid(TCA)cycle(MDH2,SUCLA2,and SUCLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13Cuniformely labeled glucose showed that TCA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TCA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramchol in 0.1MCD fed mice in a dose-dependent manner,showing normalization of glucose,G6P,F6P,UDP-glucose,and Rbl5P/Xyl5P.CONCLUSION Aramchol exerts its effect on glucose and lipid metabolism in NASH through activation of AMPK and inhibition of mTORC1,which in turn activate FAβ-oxidation and oxidative phosphorylation.
文摘Abdominal involvement in angioedema is often a challenge to diagnose.Acute onset abdominal pain is its most common presenting symptom,and misdiagnosis may lead to unnecessary surgical intervention.Familiarity with the types and presentations of angioedema can be invaluable to clinicians as they consider the differential diagnoses of a patient presenting with abdominal pain. Detailed personal and family histories,careful physical examination of the patient,combined with knowledge of angioedema types,can help clinicians perform their diagnostic evaluation.An accurate diagnosis is essential in order to provide appropriate treatment to patients with angioedema.Depending upon the diagnosis,treatment may be the avoidance of provoking factors(such as allergens or medications),inhibiting histamine-provoked reactions,or treating C1 esterase inhibitor deficiency.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;"><strong><em>Background:</em></strong> Very limited data are available regarding the association of vitamin D with glycemic status among adults with newly detected type 2 diabetes mellitus (T2DM) in Bangladesh. <strong><em>Objectives:</em></strong> To determine vitamin D status and its association with glycemic status in Bangladeshi adults with newly detected T2DM. <strong><em>Materials and Methods:</em></strong> This cross-sectional study was carried out in 102 newly detected T2DM diagnosed on the basis of the American Diabetes Association 2017 criteria (age: 42.95 ± 10.68 yrs.;m/f: 44/58) and equal number of age and sex matched controls (age: 40.43 ± 11.04 years) recruited consecutively from the Department of Endocrinology, B中央人民政府 to measure serum vitamin D by high performance liquid chromatography method. <strong><em>Results:</em></strong> Both vitamin D deficiency (<20 ng/ml) (87.3% vs. 74.5%, <em>p </em>< 0.03) and severe vitamin D deficiency (<10 ng/ml) (56.2% vs. 26.3%, <em>p</em> < 0.001) were significantly higher in people with T2DM than control population. The mean level of 25(OH)D was significantly lower in adults with T2DM than control population (12.41 ± 6.85 ng/ml vs. 15.74 ± 6.25 ng/ml, <em>p</em> < 0.001). A significant inverse correlation was observed between vitamin D & HbA<span style="white-space:nowrap;"><sub>1</sub></span>c (r = <span style="white-space:nowrap;">-</span>0.249, <em>p</em> = 0.011) in patients with T2DM. HbA<span style="white-space:nowrap;"><sub>1</sub></span>c was linearly associated with vitamin D (<em>β </em>= <span style="white-space:nowrap;">-</span>0.26, <em>p</em> = 0.009) and severe vitamin D deficiency by binary (OR = 1.37, <em>p</em> = 0.003) and multinomial logistic regression (HbA<span style="white-space:nowrap;"><sub>1</sub></span>c ≥ 10%: OR = 4.25, <em>p </em>= 0.04) in people with T2DM after adjustment for age and BMI. <strong>Conclusions:</strong> Severe vitamin D deficiency was positively associated with T2DM and inversely associated with HbA<span style="white-space:nowrap;"><sub>1</sub></span>c in patients with newly detected T2DM.</span> </div>
文摘Hereditary angioedema is a rare but life-threatening disease, usually resulting from upper respiratory tract traumas and stress. In this case report, we present the management of a 14-year-old female patient who was diagnosed with hereditary angioedema and scheduled to undergo transurethral resection of bladder (TURB) procedure for bladder tumor. She was on prophylactic danazol treatment and prior to the operation the dose of danazol was increased. On the day of the operation, patient was given C1-IHN concentrate and was sedated. In conclusion, hereditary angioedema is a rare disease in which multidisciplinary and aggressive approach during anesthesia would yield successful results.
基金This study was supported by grants from Peking University Center for Human Disease Genomics (No. 2001-2) and the National Natural Science Foundation of China (No. 30471832).
文摘Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutation was identified in 6 （9.2%） patients. The genotypes of 52 patients remained unknown. Conclusions Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.
