scholarly journals Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

2020 ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Study Results ◽  
Genes Encoding ◽  
Urine Disease

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. Results: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs*13, p.Phe149Cysfs*9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. Conclusion: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

scholarly journals Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

2020 ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Study Results ◽  
Genes Encoding ◽  
Urine Disease

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. Results: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs*13, p.Phe149Cysfs*9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. Conclusion: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

scholarly journals Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
In Silico Analysis ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Study Results ◽  
Urine Disease

Abstract Background Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. Results Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. Conclusion Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

scholarly journals Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

2019 ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
In Silico Analysis ◽  
Cross Sectional Study ◽  
Clinical Severity ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Pathogenic Variants ◽  
Study Results ◽  
Urine Disease

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving PCR and sequencing. Results: Nine new variants predicted as pathogenic were found between 30 variants identified in the 21 patients analyzed: two in the BCKDHA gene (p.Gly56Arg, and p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs*13, p.Phe149Cysfs*9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and four variants showed no pathogenicity according to in silico analysis. Conclusion: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

scholarly journals Maple Syrup Urine Disease in Brazilian Patients: Variants and Clinical Phenotype Heterogeneity

2020 ◽  
Author(s):  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
Adriana Aparecida Marques ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
In Silico Analysis ◽  
Clinical Severity ◽  
Inborn Errors ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Molecular Features ◽  
Study Results ◽  
Urine Disease ◽  
Branched Chain

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA , BCKDHB , DBT , and DLD genes. MSUD is predominantly caused by Variants in BCKDHA , BCKDHB , and DBT genes encoding the E1α, E1β, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA , BCKDHB , and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving PCR and sequencing. Results: Nine new variants predicted as pathogenic were found between 30 variants identified in the 21 patients analyzed: two in the BCKDHA gene (p.Gly56Arg, and p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs*13, p.Phe149Cysfs*9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and four variants showed no pathogenicity according to in silico analysis. Conclusion: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity. Keywords: inborn errors of metabolism; maple syrup urine disease; branched-chain amino acids; valine; leucine; isoleucine.

scholarly journals Identification of Four New Mutations in Chilean Patients with Various Forms of Maple Syrup Urine Disease and Genotype-Phenotype Correlations

2019 ◽  
Author(s):  
Diana Ruffato Resende Campanholi ◽  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Point Mutations ◽  
Cross Sectional Study ◽  
Inborn Errors ◽  
Cross Sectional ◽  
Maple Syrup ◽  
Pathogenic Mutations ◽  
Genes Encoding ◽  
Urine Disease ◽  
Branched Chain

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes in a cohort of Chilean MSUD patients, and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 18 MSUD patients was carried out using PCR and DNA sequencing. Results: Four new pathogenic mutations were identified in the 18 patients that were analyzed: one in BCKDHA (p.Thr338Ile); two in BCKDHB (p.Gly336Ser e p.Pro240Thr); and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in the analyzed patients have been described previously. Conclusion: There were no correlations observed between genotypes and phenotypes. Thus, if MSUD is diagnosed more promptly, such as in neonatal screening, it might be possible to establish genotype-phenotype relationships more efficiently. Keywords: inborn errors of metabolism; maple syrup urine disease; branched-chain amino acids; valine; leucine; isoleucine.

scholarly journals Identification of Four Novel Mutations in Chilean Patients with Various Forms of Maple Syrup Urine Disease 

2020 ◽  
Author(s):  
Diana Ruffato Resende Campanholi ◽  
Ana Vitoria Barban Margutti ◽  
Wilson Araújo Silva ◽  
Daniel Fantozzi Garcia ◽  
Greice Andreotti de Molfetta ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Point Mutations ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Inherited Metabolic Disorder ◽  
Maple Syrup ◽  
Pathogenic Mutations ◽  
Urine Disease ◽  
Branched Chain ◽  
Deficient Activity

Abstract Background: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1β, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.Results: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously.Conclusion: There were no correlations between the genotype and phenotype of the patients. Thus, if MSUD is diagnosed earlier, with a neonatal screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.

Clinical, Biochemical, Molecular, and Therapeutic Analysis of Maple Syrup Urine Disease in Upper Egypt

2020 ◽  
Author(s):  
Marwa A. Dahpy ◽  
Tahia H. Saleem ◽  
Osama M. El-Asheer ◽  
Ahmed Abd ELrasoul ◽  
Amir M. Abo Elgeit
Keyword(s):  
Maple Syrup Urine Disease ◽  
Homozygous Mutation ◽  
Laboratory Findings ◽  
Upper Egypt ◽  
Maple Syrup ◽  
Treatment Regimens ◽  
Genes Encoding ◽  
Urine Disease ◽  
Branched Chain

AbstractMaple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in any of the genes encoding for the branched-chain keto dehydrogenase (BCKDH) components. This study screened MSUD patients throughout the whole Upper Egypt describing their symptoms, clinical and laboratory findings, genetic studies, and their treatment, with a 6-month follow-up for their responses. Screening identified three children with MSUD. Homozygous mutation in R195Q single nucleotide polymorphism (SNP) within the BCKDHA gene was found with the second MSUD patient. Follow-up for 6 months to assess the treatment regimens and progression of cases demonstrated that early treatment regimens including a dietary restriction of branched-chain amino acids with L-Carnitine administration could prevent MSUD-associated intellectual disabilities. It was concluded that R195Q SNP is pathogenic, and it may cause inherited forms of MSUD in some patients. MSUD cases have rarely been reported; so these findings will be highly useful for future cases of MSUD in the Upper Egyptian population.

scholarly journals Genetic analysis by targeted next-generation sequencing and novel variation identification of maple syrup urine disease in Chinese Han population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaohua Fang ◽  
Xiaofan Zhu ◽  
Yin Feng ◽  
Ying Bai ◽  
Xuechao Zhao ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Mainland China ◽  
Autosomal Recessive Disorder ◽  
Chinese Han ◽  
Maple Syrup ◽  
Targeted Next Generation Sequencing ◽  
Pathogenic Variants ◽  
Targeted Ngs ◽  
Urine Disease ◽  
Branched Chain

AbstractMaple syrup urine disease (MSUD) is a rare autosomal recessive disorder that affects the degradation of branched chain amino acids (BCAAs). Only a few cases of MSUD have been documented in Mainland China. In this report, 8 patients (4 females and 4 males) with MSUD from 8 unrelated Chinese Han families were diagnosed at the age of 6 days to 4 months. All the coding regions and exon/intron boundaries of BCKDHA, BCDKHB, DBT and DLD genes were analyzed by targeted NGS in the 8 MSUD pedigrees. Targeted NGS revealed 2 pedigrees with MSUD Ia, 5 pedigrees with Ib, 1 pedigree with MSUD II. Totally, 13 variants were detected, including 2 variants (p.Ala216Val and p.Gly281Arg) in BCKDHA gene, 10 variants (p.Gly95Ala, p.Ser171Pro, p.Phe175Leu, p.Arg183Trp, p.Lys222Thr, p.Arg285Ter, p.Arg111Ter, p.S184Pfs*46, p.Arg170Cys, p.I160Ffs*25) in BCKDHB gene, 1 variant (p.Arg431Ter) in DBT gene. In addition, 4 previously unidentified variants (p.Gly281Arg in BCKDHA gene, p.Ser171Pro, p.Gly95Ala and p.Lys222Thr in BCKDHB gene) were identified. NGS plus Sanger sequencing detection is effective and accurate for gene diagnosis. Computational structural modeling indicated that these novel variations probably affect structural stability and considered as likely pathogenic variants.

Fatal course of maple syrup urine disease (MSUD) encephalopathy in a 6 year old boy with characteristic MRI-changes

2006 ◽  
Vol 37 (03) ◽  
Author(s):  
V Boda ◽  
S Vlaho ◽  
S Dittrich ◽  
M Baz Bartels ◽  
S Parbel ◽  
...  
Keyword(s):  
Maple Syrup Urine Disease ◽  
Maple Syrup ◽  
Fatal Course ◽  
Urine Disease ◽  
Mri Changes

ASSESSMENT OF SKILLED BIRTH ATTENDANTS REGARDING HELPING BABIES BREATH INTERVENTION TO IMPROVE NEWBORN CARE IN RURAL DISTRICT OF SINDH

1970 ◽  
Vol 7 (1) ◽  
pp. 48-53
Author(s):  
Sheh Mureed ◽  
Muhammad Hassan Gandro ◽  
Walid Hassan
Keyword(s):  
Newborn Care ◽  
Cross Sectional Study ◽  
Vital Role ◽  
Skilled Birth Attendants ◽  
Cross Sectional ◽  
Neonatal Deaths ◽  
Birth Attendants ◽  
Study Results ◽  
Knowledge And Practice ◽  
Labour Room

Background: Globally, 3.1 million newborn deaths occur every year out of these estimated 400,000 neonatal deaths occur in Pakistan. All neonatal deaths 99% take place in poorest region and countries of the world, usually within hours of birth; mostly the cause of neonatal deaths is hypoxia. To access knowledge and practice of SBAs regarding HBB and to access the availability of equipments required for HBB. Methods: Descriptive Cross-Sectional Study on SBAs as trained in HBB. All 46 SBAs trained on HBB working in Labour room eight rural Health centers, four Taluka, One district Head Quarter Health Facilities and thirteen Mlbcs of the district, were included in the sample for study. All 41 SBAs were trained on HBB participated in the study. Results: Mean age of 30 years. Out of total 41 participants 25 were working in B-EmoNC (61%), 3in C-EmoNC (7.3%) and 13 in mid wife laid birth Centre (MLBC) or birth station (31.7%). About 92.7% of participants said that main purpose of HBB training is to decrease the NMR by improving newborn care. Drying of newborn is 82.7%, hand washing is 95.12% and 85.3% of the study participants said that they gave 30-40 breaths per minutes. Cord clamp and pair of ties was accessible to 85% of participants versus 14.3% who reported it's not accessible. Almost one quarter (34.1%) participants have low knowledge and practice. Knowledge and training had significant effect on the overall practices of the skilled birth attendants for skilled birth deliveries and reduce the neonatal deaths (P <0.001). Conclusion: Tools play a vital role for the implication of the knowledge into practices and tools were available almost to every participant. Although few barriers also identified for the less application of the helping hand babies trainings in the community.

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